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Cell death in skin function, inflammation, and disease Biochem. J. (IF 3.766) Pub Date : 2022-08-12 Anderton, Holly, Alqudah, Suhaib
Cell death is an essential process that plays a vital role in restoring and maintaining skin homeostasis. It supports recovery from acute injury and infection and regulates barrier function and immunity. Cell death can also provoke inflammatory responses. Loss of cell membrane integrity with lytic forms of cell death can incite inflammation due to the uncontrolled release of cell contents. Excessive
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The cross-talk of autophagy and apoptosis in breast carcinoma: implications for novel therapies? Biochem. J. (IF 3.766) Pub Date : 2022-07-29 Seyrek, Kamil, Wohlfromm, Fabian, Espe, Johannes, Lavrik, Inna N.
Breast cancer is still the most common cancer in women worldwide. Resistance to drugs and recurrence of the disease are two leading causes of failure in treatment. For a more efficient treatment of patients, the development of novel therapeutic regimes is needed. Recent studies indicate that modulation of autophagy in concert with apoptosis induction may provide a promising novel strategy in breast
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Structural and functional characterisation of a stable, broad-specificity multimeric sialidase from the oral pathogen Tannerella forsythia. Biochem. J. (IF 3.766) Pub Date : 2022-08-02 Marianne J Satur,Paulina Urbanowicz,Daniel R Spencer,John B Rafferty,Graham Philip Stafford
Sialidases are glycosyl hydrolase enzymes targeting the glycosidic bond between terminal sialic acids and underlying sugars. The NanH sialidase of Tannerella forsythia, one of the bacteria associated with severe periodontal disease plays a role in virulence. Here we show that this broad-specificity enzyme (but higher affinity for α2,3 over α2,6 linked sialic acids) digests complex glycans but not those
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Identification of ELK1 interacting peptide segments in the androgen receptor Biochem. J. (IF 3.766) Pub Date : 2022-07-29 Soave, Claire, Ducker, Charles, Kim, Seongho, Strahl, Thomas, Rosati, Rayna, Huang, Yanfang, Shaw, Peter E., Ratnam, Manohar
Prostate cancer (PCa) growth requires tethering of the androgen receptor (AR) to chromatin by the ETS domain transcription factor ELK1 to coactivate critical cell proliferation genes. Disruption of the ELK1–AR complex is a validated potential means of therapeutic intervention in PCa. AR associates with ELK1 by coopting its two ERK docking sites, through the amino-terminal domain (A/B domain) of AR
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Gain of function of a metalloproteinase associated with multiple myeloma, bicuspid aortic valve, and Von Hippel–Lindau syndrome Biochem. J. (IF 3.766) Pub Date : 2022-07-29 Snipas, Scott J., Jappelli, Roberto, Torkamani, Ali, Paternostro, Giovanni, Salvesen, Guy S.
A patient diagnosed with multiple myeloma, bicuspid aortic valve, and Von Hippel–Lindau syndrome underwent whole-exome sequencing seeking a unified genetic cause for these three pathologies. The patient possessed a single-point mutation of arginine to cysteine (R24C) in the N-terminal region(pro-domain) of matrix metalloproteinase 9 (MMP-9). The pro-domain interacts with the catalytic site of this
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Vitamin K3 inhibits FtsZ assembly, disrupts the Z-ring in Streptococcus pneumoniae and displays anti-pneumococcal activity Biochem. J. (IF 3.766) Pub Date : 2022-07-29 Pushpakaran, Athira, Battaje, Rachana Rao, Panda, Dulal
The respiratory pathogen, Streptococcus pneumoniae has acquired multiple-drug resistance over the years. An attractive strategy to combat pneumococcal infection is to target cell division to inhibit the proliferation of S. pneumoniae. This work presents Vitamin K3 as a potential anti-pneumococcal drug that targets FtsZ, the master coordinator of bacterial cell division. Vitamin K3 strongly inhibited
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Binding of the Mycobacterium tuberculosis EccCb1 ATPase double hexameric ring to the EsxAB virulence factor is enhanced by ATP Biochem. J. (IF 3.766) Pub Date : 2022-07-29 Bandyopadhyay, Arkita, Kumar, Ramesh, Singh, Jyotsna, Saxena, Ajay K.
The EccC enzyme of Mycobacterium tuberculosis ESX-1 secretion system is involved in EsxAB virulence factor secretion and offers an attractive target for antivirulence inhibitors development against M. tuberculosis. The EccCb1 polypeptide of the EccC enzyme contains two Ftsk/SpoIIIE type ATPase domains (D2 and D3) and binds to the EsxAB factor at the C-terminal region of the D3 domain. In the current
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Highly sensitive tryptophan fluorescence probe for detecting rhythmic conformational changes of KaiC in the cyanobacterial circadian clock system Biochem. J. (IF 3.766) Pub Date : 2022-07-29 Mukaiyama, Atsushi, Furuike, Yoshihiko, Yamashita, Eiki, Akiyama, Shuji
KaiC, a core protein of the cyanobacterial circadian clock, consists of an N-terminal CI domain and a C-terminal CII domain, and assembles into a double-ring hexamer upon binding with ATP. KaiC rhythmically phosphorylates and dephosphorylates its own two adjacent residues Ser431 and Thr432 at the CII domain with a period of ∼24 h through assembly and disassembly with the other clock proteins, KaiA
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Expression of Concern: N-terminal chimaeras with signal sequences enhance the functional expression and alter the subcellular localization of heterologous membrane-bound inorganic pyrophosphatases in yeast Biochem. J. (IF 3.766) Pub Date : 2022-07-29
The Editorial Office has been made aware of potential concerns surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.
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The function of BK channels extracted and purified within SMALPs. Biochem. J. (IF 3.766) Pub Date : 2022-08-12 Jaimin H Patel,Naomi L Pollock,Jacqueline Maher,Alice J Rothnie,Marcus C Allen
Human BK channels are large voltage and Ca2+-activated K+ channels, involved in several important functions within the body. The core channel is a tetramer of α subunits, and its function is modulated by the presence of β and γ accessory subunits. BK channels composed of α subunits, as well as BK channels composed of α and β1 subunits, were successfully solubilised from HEK cells with styrene maleic
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Cryo-EM structures of the Synechocystis sp. PCC 6803 cytochrome b6f complex with and without the regulatory PetP subunit Biochem. J. (IF 3.766) Pub Date : 2022-07-15 Proctor, Matthew S., Malone, Lorna A., Farmer, David A., Swainsbury, David J.K., Hawkings, Frederick R., Pastorelli, Federica, Emrich-Mills, Thomas Z., Siebert, C. Alistair, Hunter, C. Neil, Johnson, Matthew P., Hitchcock, Andrew
In oxygenic photosynthesis, the cytochrome b6f (cytb6f) complex links the linear electron transfer (LET) reactions occurring at photosystems I and II and generates a transmembrane proton gradient via the Q-cycle. In addition to this central role in LET, cytb6f also participates in a range of processes including cyclic electron transfer (CET), state transitions and photosynthetic control. Many of the
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The mitochondrial translocator protein (TSPO): a key multifunctional molecule in the nervous system Biochem. J. (IF 3.766) Pub Date : 2022-07-15 El Chemali, Léa, Akwa, Yvette, Massaad-Massade, Liliane
Translocator protein (TSPO, 18 kDa), formerly known as peripheral benzodiazepine receptor, is an evolutionary well-conserved protein located on the outer mitochondrial membrane. TSPO is involved in a variety of fundamental physiological functions and cellular processes. Its expression levels are regulated under many pathological conditions, therefore, TSPO has been proposed as a tool for diagnostic
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Characterization of functionally deficient SIM2 variants found in patients with neurological phenotypes Biochem. J. (IF 3.766) Pub Date : 2022-07-15 Button, Emily L., Rossi, Joseph J., McDougal, Daniel P., Bruning, John B., Peet, Daniel J., Bersten, David C., Rosenfeld, Jill A., Whitelaw, Murray L.
Single-minded 2 (SIM2) is a neuron-enriched basic Helix–Loop–Helix/PER–ARNT–SIM (bHLH/PAS) transcription factor essential for mammalian survival. SIM2 is located within the Down syndrome critical region (DSCR) of chromosome 21, and manipulation in mouse models suggests Sim2 may play a role in brain development and function. During the screening of a clinical exome sequencing database, nine SIM2 non-synonymous
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PKN2 deficiency leads both to prenatal ‘congenital’ cardiomyopathy and defective angiotensin II stress responses Biochem. J. (IF 3.766) Pub Date : 2022-07-15 Marshall, Jacqueline J.T., Cull, Joshua J., Alharbi, Hajed O., Zaw Thin, May, Cooper, Susanna T.E., Barrington, Christopher, Vanyai, Hannah, Snoeks, Thomas, Siow, Bernard, Suáarez-Bonnet, Alejandro, Herbert, Eleanor, Stuckey, Daniel J., Cameron, Angus J.M., Prin, Fabrice, Cook, Andrew C., Priestnall, Simon L., Chotani, Sonia, Rackham, Owen J. L., Meijles, Daniel N., Mohun, Tim, Clerk, Angela, Parker
The protein kinase PKN2 is required for embryonic development and PKN2 knockout mice die as a result of failure in the expansion of mesoderm, cardiac development and neural tube closure. In the adult, cardiomyocyte PKN2 and PKN1 (in combination) are required for cardiac adaptation to pressure-overload. The specific role of PKN2 in contractile cardiomyocytes during development and its role in the adult
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CORM-3 induces DNA damage through Ru(II) binding to DNA Biochem. J. (IF 3.766) Pub Date : 2022-07-15 Lyon, Rhiannon F., Southam, Hannah M., Trevitt, Clare R., Liao, Chunyan, El-Khamisy, Sherif F., Poole, Robert K., Williamson, Mike P.
When the ‘CO-releasing molecule-3’, CORM-3 (Ru(CO)3Cl(glycinate)), is dissolved in water it forms a range of ruthenium complexes. These are taken up by cells and bind to intracellular ligands, notably thiols such as cysteine and glutathione, where the Ru(II) reaches high intracellular concentrations. Here, we show that the Ru(II) ion also binds to DNA, at exposed guanosine N7 positions. It therefore
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Binding partners regulate unfolding of myosin VI to activate the molecular motor Biochem. J. (IF 3.766) Pub Date : 2022-07-15 dos Santos, Ália, Fili, Natalia, Hari-Gupta, Yukti, Gough, Rosemarie E., Wang, Lin, Martin-Fernandez, Marisa, Aaron, Jesse, Wait, Eric, Chew, Teng-Leong, Toseland, Christopher P.
Myosin VI is the only minus-end actin motor and it is coupled to various cellular processes ranging from endocytosis to transcription. This multi-potent nature is achieved through alternative isoform splicing and interactions with a network of binding partners. There is a complex interplay between isoforms and binding partners to regulate myosin VI. Here, we have compared the regulation of two myosin
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Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism? Biochem. J. (IF 3.766) Pub Date : 2022-06-30 Szibor, Marten, Schenkl, Christina, Barsottini, Mario R. O., Young, Luke, Moore, Anthony L.
Some of the most threatening human diseases are due to a blockage of the mitochondrial electron transport chain (ETC). In a variety of plants, fungi, and prokaryotes, there is a naturally evolved mechanism for such threats to viability, namely a bypassing of the blocked portion of the ETC by alternative enzymes of the respiratory chain. One such enzyme is the alternative oxidase (AOX). When AOX is
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Deciphering signal transduction networks in the liver by mechanistic mathematical modelling Biochem. J. (IF 3.766) Pub Date : 2022-06-30 D’Alessandro, Lorenza A., Klingmüller, Ursula, Schilling, Marcel
In health and disease, liver cells are continuously exposed to cytokines and growth factors. While individual signal transduction pathways induced by these factors were studied in great detail, the cellular responses induced by repeated or combined stimulations are complex and less understood. Growth factor receptors on the cell surface of hepatocytes were shown to be regulated by receptor interactions
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Distinct interactors define the p63 transcriptional signature in epithelial development or cancer Biochem. J. (IF 3.766) Pub Date : 2022-06-30 Pecorari, Rosalba, Bernassola, Francesca, Melino, Gerry, Candi, Eleonora
The TP63 is an indispensable transcription factor for development and homeostasis of epithelia and its derived glandular tissue. It is also involved in female germline cell quality control, muscle and thymus development. It is expressed as multiple isoforms transcribed by two independent promoters, in addition to alternative splicing occurring at the mRNA 3′-UTR. Expression of the TP63 gene, specifically
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Deafness-related protein PDZD7 forms complex with the C-terminal tail of FCHSD2 Biochem. J. (IF 3.766) Pub Date : 2022-06-30 Wang, Huang, Zhao, Dange, Du, Haibo, Zhai, Xiaoyan, Wu, Shaoxuan, Lin, Lin, Xu, Zhigang, Lu, Qing
In cochlea, deafness-related protein PDZD7 is an indispensable component of the ankle link complex, which is critical for the maturation of inner-ear hair cell for sound perception. Ankle links, connecting the different rows of cochlear stereocilia, are essential for the staircase-like development of stereocilia. However, the molecular mechanism of how PDZD7 governs stereociliary development remains
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Anti-tumor and anti-metastatic activity of the FGF2 118–126 fragment dependent on the loop structure Biochem. J. (IF 3.766) Pub Date : 2022-06-30 Allahmoradi, Hossein, Asghari, S. Mohsen, Ahmadi, Atieh, Assareh, Elham, Nazari, Mahboobeh
Fibroblast Growth Factor/FGF Receptor 1 (FGF2/FGFR1) system regulates the growth and metastasis of different cancers. Inhibition of this signaling pathway is an attractive target for cancer therapy. Here, we aimed to reproduce the 118–126 fragment of FGF2 to interfere with the FGF2–FGFR1 interaction. To determine whether the loop structure affects the function of this fragment, we compared cyclic (disulfide-bonded)
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Molecular basis of Tick Born encephalitis virus NS5 mediated subversion of apico-basal cell polarity signalling Biochem. J. (IF 3.766) Pub Date : 2022-06-30 Javorsky, Airah, Humbert, Patrick O., Kvansakul, Marc
The Scribble (Scrib) protein is a conserved cell polarity regulator with anti-tumorigenic properties. Viruses like the Tick-born encephalitis virus (TBEV) target Scribble to establish a cellular environment supporting viral replication, which is ultimately associated with poor prognosis upon infection. The TBEV NS5 protein has been reported to harbour both an internal as well as a C-terminal PDZ binding
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Inhibition of basal and glucagon-induced hepatic glucose production by 991 and other pharmacological AMPK activators Biochem. J. (IF 3.766) Pub Date : 2022-06-30 Johanns, Manuel, Corbet, Cyril, Jacobs, Roxane, Drappier, Melissa, Bommer, Guido T., Herinckx, Gaëtan, Vertommen, Didier, Tajeddine, Nicolas, Young, David, Messens, Joris, Feron, Olivier, Steinberg, Gregory R., Hue, Louis, Rider, Mark H.
Pharmacological AMPK activation represents an attractive approach for the treatment of type 2 diabetes (T2D). AMPK activation increases skeletal muscle glucose uptake, but there is controversy as to whether AMPK activation also inhibits hepatic glucose production (HGP) and pharmacological AMPK activators can have off-target effects that contribute to their anti-diabetic properties. The main aim was
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Towards 'end-to-end' analysis and understanding of biological timecourse data. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Siddhartha G Jena,Alexander G Goglia,Barbara E Engelhardt
Petabytes of increasingly complex and multidimensional live cell and tissue imaging data are generated every year. These videos hold large promise for understanding biology at a deep and fundamental level, as they capture single-cell and multicellular events occurring over time and space. However, the current modalities for analysis and mining of these data are scattered and user-specific, preventing
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A structural approach to understanding enzymatic regulation of chemical reaction networks. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Atsushi Mochizuki
In living cells, chemical reactions are connected by sharing their products and substrates, and form complex systems, i.e. chemical reaction network. One of the largest missions in modern biology is to understand behaviors of such systems logically based on information of network structures. However, there are series of obstacles to study dynamical behaviors of complex network systems in biology. For
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NUCKS1 is a highly modified, chromatin-associated protein involved in a diverse set of biological and pathophysiological processes Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Østvold, Anne Carine, Grundt, Kirsten, Wiese, Claudia
The Nuclear Casein and Cyclin-dependent Kinase Substrate 1 (NUCKS1) protein is highly conserved in vertebrates, predominantly localized to the nucleus and one of the most heavily modified proteins in the human proteome. NUCKS1 expression is high in stem cells and the brain, developmentally regulated in mice and associated with several diverse malignancies in humans, including cancer, metabolic syndrome
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Characterization of uridine-cytidine kinase like-1 nucleoside kinase activity and its role in tumor growth Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Matchett, Emily C., Ambrose, Elise C., Kornbluth, Jacki
Uridine-cytidine kinase like-1 (UCKL-1) is a largely uncharacterized protein with high sequence similarity to other uridine-cytidine kinases (UCKs). UCKs play an important role in the pyrimidine salvage pathway, catalyzing the phosphorylation of uridine and cytidine to UMP and CMP, respectively. Only two human UCKs have been identified, UCK1 and UCK2. Previous studies have shown both enzymes phosphorylate
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NAD-catabolizing ectoenzymes of Schistosoma mansoni Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Nation, Catherine S., Da'Dara, Akram A., Skelly, Patrick J.
Infection with schistosomes (blood flukes) can result in the debilitating disease schistosomiasis. These parasites survive in their host for many years, and we hypothesize that proteins on their tegumental surface, interacting with the host microenvironment, facilitate longevity. One such ectoenzyme — the nucleotide pyrophosphatase/phosphodiesterase SmNPP5 can cleave ADP (to prevent platelet aggregation)
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Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Ovens, Ashley J., Gee, Yi Sing, Ling, Naomi X.Y., Yu, Dingyi, Hardee, Justin P., Chung, Jin D., Ngoei, Kevin R.W., Waters, Nicholas J., Hoffman, Nolan J., Scott, John W., Loh, Kim, Spengler, Katrin, Heller, Regine, Parker, Michael W., Lynch, Gordon S., Huang, Fei, Galic, Sandra, Kemp, Bruce E., Baell, Jonathan B., Oakhill, Jonathan S., Langendorf, Christopher G.
The AMP-activated protein kinase (AMPK) αβγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2β2γ1 isoform combination
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Endogenous glutamine is rate-limiting for anti-CD3 and anti-CD28 induced CD4+ T-cell proliferation and glycolytic activity under hypoxia and normoxia Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Wik, Jonas A., Chowdhury, Azazul, Kolan, Shrikant, Bastani, Nasser E., Li, Gaoyang, Alam, Kazi, Grimolizzi, Franco, Skålhegg, Bjørn S.
To meet the demand for energy and biomass, T lymphocytes (T cells) activated to proliferation and clonal expansion, require uptake and metabolism of glucose (Gluc) and the amino acid (AA) glutamine (Gln). Whereas exogenous Gln is converted to glutamate (Glu) by glutaminase (GLS), Gln is also synthesized from the endogenous pool of AA through Glu and activity of glutamine synthase (GS). Most of this
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Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Duan, Xiaowen, Norris, Dougall M., Humphrey, Sean J., Yang, Pengyi, Cooke, Kristen C., Bultitude, Will P., Parker, Benjamin L., Conway, Olivia J., Burchfield, James G., Krycer, James R., Brodsky, Frances M., James, David E., Fazakerley, Daniel J.
Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine
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Correction: Rivastigmine attenuates the Alzheimer's disease related protein degradation and apoptotic neuronal death signaling Biochem. J. (IF 3.766) Pub Date : 2022-06-17
The authors of the original article “Rivastigmine attenuates the Alzheimer's disease related protein degradation and apoptotic neuronal death signalling” (Biochem J (2021) 478 (7): 1435–1451; https://doi.org/10.1042/BCJ20200754.) would like to correct an error in Figure 4. The authors have identified an error in Figure 4 related to two statistical asterisks (*). As reported in the result section, the
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NUCKS1 is a highly modified, chromatin-associated protein involved in a diverse set of biological and pathophysiological processes. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Anne Carine Østvold,Kirsten Grundt,Claudia Wiese
The Nuclear Casein and Cyclin-dependent Kinase Substrate 1 (NUCKS1) protein is highly conserved in vertebrates, predominantly localized to the nucleus and one of the most heavily modified proteins in the human proteome. NUCKS1 expression is high in stem cells and the brain, developmentally regulated in mice and associated with several diverse malignancies in humans, including cancer, metabolic syndrome
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Endogenous glutamine is rate-limiting for anti-CD3 and anti-CD28 induced CD4+ T-cell proliferation and glycolytic activity under hypoxia and normoxia. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Jonas A Wik,Azazul Chowdhury,Shrikant Kolan,Nasser E Bastani,Gaoyang Li,Kazi Alam,Franco Grimolizzi,Bjørn S Skålhegg
To meet the demand for energy and biomass, T lymphocytes (T cells) activated to proliferation and clonal expansion, require uptake and metabolism of glucose (Gluc) and the amino acid (AA) glutamine (Gln). Whereas exogenous Gln is converted to glutamate (Glu) by glutaminase (GLS), Gln is also synthesized from the endogenous pool of AA through Glu and activity of glutamine synthase (GS). Most of this
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Insight into the function of a unique voltage-sensor protein (TMEM266) and its short form in mouse cerebellum Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Kawai, Takafumi, Narita, Hirotaka, Konno, Kohtarou, Akter, Sharmin, Andriani, Rizki Tsari, Iwasaki, Hirohide, Nishikawa, Shoji, Yokoi, Norihiko, Fukata, Yuko, Fukata, Masaki, Wiriyasermkul, Pattama, Kongpracha, Pornparn, Nagamori, Shushi, Takao, Keizo, Miyakawa, Tsuyoshi, Abe, Manabu, Sakimura, Kenji, Watanabe, Masahiko, Nakagawa, Atsushi, Okamura, Yasushi
Voltage-sensing proteins generally consist of voltage-sensor domains and pore-gate domains, forming the voltage-gated ion channels. However, there are several unconventional voltage-sensor proteins that lack pore-gate domains, conferring them unique voltage-sensing machinery. TMEM266, which is expressed in cerebellum granule cells, is one of the interesting voltage-sensing proteins that has a putative
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Alphabetti kinase Spaghetti: the complex roles of IKKα and β in the canonical NF-κB pathway Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Perkins, Neil D.
Numerous studies, published over many years, have established the key role that the IκB kinase (IKK) subunits, α and β, play in regulating the Nuclear Factor κB (NF-κB) pathway. This research generally concluded that their functions can be separated, with IKKβ being the critical regulator of the canonical NF-κB pathway, while IKKα functions as the key activating kinase for the non-canonical pathway
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Improved furfural tolerance in Escherichia coli mediated by heterologous NADH-dependent benzyl alcohol dehydrogenases Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Willson, Benjamin James, Herman, Reyme, Langer, Swen, Thomas, Gavin Hugh
While lignocellulose is a promising source of renewable sugars for microbial fermentations, the presence of inhibitory compounds in typical lignocellulosic feedstocks, such as furfural, has hindered their utilisation. In Escherichia coli, a major route of furfural toxicity is the depletion of NADPH pools due to its use as a substrate by the YqhD enzyme that reduces furfural to its less toxic alcohol
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The role of eIF2 phosphorylation in cell and organismal physiology: new roles for well-known actors Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Wang, Xuemin, Proud, Christopher G.
Control of protein synthesis (mRNA translation) plays key roles in shaping the proteome and in many physiological, including homeostatic, responses. One long-known translational control mechanism involves phosphorylation of initiation factor, eIF2, which is catalysed by any one of four protein kinases, which are generally activated in response to stresses. They form a key arm of the integrated stress
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No longer married to inflammasome signaling: the diverse interacting pathways leading to pyroptotic cell death Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Weir, Ashley, Vince, James E.
For over 15 years the lytic cell death termed pyroptosis was defined by its dependency on the inflammatory caspase, caspase-1, which, upon pathogen sensing, is activated by innate immune cytoplasmic protein complexes known as inflammasomes. However, this definition of pyroptosis changed when the pore-forming protein gasdermin D (GSDMD) was identified as the caspase-1 (and caspase-11) substrate required
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No longer married to inflammasome signaling: the diverse interacting pathways leading to pyroptotic cell death. Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Ashley Weir,James E Vince
For over 15 years the lytic cell death termed pyroptosis was defined by its dependency on the inflammatory caspase, caspase-1, which, upon pathogen sensing, is activated by innate immune cytoplasmic protein complexes known as inflammasomes. However, this definition of pyroptosis changed when the pore-forming protein gasdermin D (GSDMD) was identified as the caspase-1 (and caspase-11) substrate required
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Deubiquitinases in cell death and inflammation. Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Kim Newton,Alexander D Gitlin
Apoptosis, pyroptosis, and necroptosis are distinct forms of programmed cell death that eliminate infected, damaged, or obsolete cells. Many proteins that regulate or are a part of the cell death machinery undergo ubiquitination, a post-translational modification made by ubiquitin ligases that modulates protein abundance, localization, and/or activity. For example, some ubiquitin chains target proteins
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The role of eIF2 phosphorylation in cell and organismal physiology: new roles for well-known actors. Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Xuemin Wang,Christopher G Proud
Control of protein synthesis (mRNA translation) plays key roles in shaping the proteome and in many physiological, including homeostatic, responses. One long-known translational control mechanism involves phosphorylation of initiation factor, eIF2, which is catalysed by any one of four protein kinases, which are generally activated in response to stresses. They form a key arm of the integrated stress
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Characterization of uridine-cytidine kinase like-1 nucleoside kinase activity and its role in tumor growth. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Emily C Matchett,Elise C Ambrose,Jacki Kornbluth
Uridine-cytidine kinase like-1 (UCKL-1) is a largely uncharacterized protein with high sequence similarity to other uridine-cytidine kinases (UCKs). UCKs play an important role in the pyrimidine salvage pathway, catalyzing the phosphorylation of uridine and cytidine to UMP and CMP, respectively. Only two human UCKs have been identified, UCK1 and UCK2. Previous studies have shown both enzymes phosphorylate
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Insight into the function of a unique voltage-sensor protein (TMEM266) and its short form in mouse cerebellum. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Takafumi Kawai,Hirotaka Narita,Kohtarou Konno,Sharmin Akter,Rizki Tsari Andriani,Hirohide Iwasaki,Shoji Nishikawa,Norihiko Yokoi,Yuko Fukata,Masaki Fukata,Pattama Wiriyasermkul,Pornparn Kongpracha,Shushi Nagamori,Keizo Takao,Tsuyoshi Miyakawa,Manabu Abe,Kenji Sakimura,Masahiko Watanabe,Atsushi Nakagawa,Yasushi Okamura
Voltage-sensing proteins generally consist of voltage-sensor domains and pore-gate domains, forming the voltage-gated ion channels. However, there are several unconventional voltage-sensor proteins that lack pore-gate domains, conferring them unique voltage-sensing machinery. TMEM266, which is expressed in cerebellum granule cells, is one of the interesting voltage-sensing proteins that has a putative
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Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator. Biochem. J. (IF 3.766) Pub Date : 2022-06-17 Ashley J Ovens,Yi Sing Gee,Naomi X Y Ling,Dingyi Yu,Justin P Hardee,Jin D Chung,Kevin R W Ngoei,Nicholas J Waters,Nolan J Hoffman,John W Scott,Kim Loh,Katrin Spengler,Regine Heller,Michael W Parker,Gordon S Lynch,Fei Huang,Sandra Galic,Bruce E Kemp,Jonathan B Baell,Jonathan S Oakhill,Christopher G Langendorf
The AMP-activated protein kinase (AMPK) αβγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2β2γ1 isoform combination
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No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Mailliot, Justine, Vivoli-Vega, Mirella, Schaffitzel, Christiane
Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3′-untranslated region and the presence of an exon-junction complex
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No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors. Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Justine Mailliot,Mirella Vivoli-Vega,Christiane Schaffitzel
Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3'-untranslated region and the presence of an exon-junction complex
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Alveolar cells in the mammary gland: lineage commitment and cell death. Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Christine J Watson
The mammary gland provides a spectacular example of physiological cell death whereby the cells that produce milk during lactation are removed swiftly, efficiently, and without inducing inflammation upon the cessation of lactation. The milk-producing cells arise primarily during pregnancy and comprise the alveolar lineage that is specified by signalling pathways and factors that are activated in response
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RIP1 post-translational modifications Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Varfolomeev, Eugene, Vucic, Domagoj
Receptor interacting protein 1 (RIP1) kinase is a critical regulator of inflammation and cell death signaling, and plays a crucial role in maintaining immune responses and proper tissue homeostasis. Mounting evidence argues for the importance of RIP1 post-translational modifications in control of its function. Ubiquitination by E3 ligases, such as inhibitors of apoptosis (IAP) proteins and LUBAC, as
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Citrylglutamate synthase deficient male mice are subfertile with impaired histone and transition protein 2 removal in late spermatids Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Wang-Eckhardt, Lihua, Sylvester, Marc, Becker, Ivonne, Allam, Jean-Pierre, Eckhardt, Matthias
Chromatin remodelling in spermatids is an essential step in spermiogenesis and involves the exchange of most histones by protamines, which drives chromatin condensation in late spermatids. The gene Rimklb encodes a citrylglutamate synthase highly expressed in testes of vertebrates and the increase of its reaction product, β-citrylglutamate, correlates in time with the appearance of spermatids. Here
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Improved furfural tolerance in Escherichia coli mediated by heterologous NADH-dependent benzyl alcohol dehydrogenases. Biochem. J. (IF 3.766) Pub Date : 2022-05-27 Benjamin James Willson,Reyme Herman,Swen Langer,Gavin Hugh Thomas
While lignocellulose is a promising source of renewable sugars for microbial fermentations, the presence of inhibitory compounds in typical lignocellulosic feedstocks, such as furfural, has hindered their utilisation. In Escherichia coli, a major route of furfural toxicity is the depletion of NADPH pools due to its use as a substrate by the YqhD enzyme that reduces furfural to its less toxic alcohol
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Integration of machine learning with computational structural biology of plants Biochem. J. (IF 3.766) Pub Date : 2022-04-29 Chen, Jiming, Shukla, Diwakar
Computational structural biology of proteins has developed rapidly in recent decades with the development of new computational tools and the advancement of computing hardware. However, while these techniques have widely been used to make advancements in human medicine, these methods have seen less utilization in the plant sciences. In the last several years, machine learning methods have gained popularity
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Sialylation-dependent pharmacokinetics and differential complement pathway inhibition are hallmarks of CR1 activity in vivo. Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Sandra Wymann,Marcel Mischnik,David Leong,Subhajit Ghosh,Xiahui Tan,Helen Cao,Benjamin Kuehnemuth,Glenn A Powers,Partho Halder,Mitchell J de Souza,Hannah S James,Vesna Tomasetig,Holger Lind,Paolo Rossato,Catherine M Owczarek,Saw Yen Ow,Steven K Dower,Adriana Baz Morelli,Tony Rowe,Matthew P Hardy
Human Complement Receptor 1 (HuCR1) is a potent membrane-bound regulator of complement both in vitro and in vivo, acting via interaction with its ligands C3b and C4b. Soluble versions of HuCR1 have been described such as TP10, the recombinant full-length extracellular domain, and more recently CSL040, a truncated version lacking the C-terminal long homologous repeat domain D (LHR-D). However, the role
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Quantitative live-cell imaging of GPCR downstream signaling dynamics Biochem. J. (IF 3.766) Pub Date : 2022-04-29 Tany, Ryosuke, Goto, Yuhei, Kondo, Yohei, Aoki, Kazuhiro
G-protein-coupled receptors (GPCRs) play an important role in sensing various extracellular stimuli, such as neurotransmitters, hormones, and tastants, and transducing the input information into the cell. While the human genome encodes more than 800 GPCR genes, only four Gα-proteins (Gαs, Gαi/o, Gαq/11, and Gα12/13) are known to couple with GPCRs. It remains unclear how such divergent GPCR information
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Development of a colorimetric assay for the detection of SARS-CoV-2 3CLpro activity Biochem. J. (IF 3.766) Pub Date : 2022-04-29 Garland, Gavin D., Harvey, Robert F., Mulroney, Thomas E., Monti, Mie, Fuller, Stewart, Haigh, Richard, Gerber, Pehuén Pereyra, Barer, Michael R., Matheson, Nicholas J., Willis, Anne E.
Diagnostic testing continues to be an integral component of the strategy to contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) global pandemic, the causative agent of Coronavirus Disease 2019 (COVID-19). The SARS-CoV-2 genome encodes the 3C-like protease (3CLpro) which is essential for coronavirus replication. This study adapts an in vitro colorimetric gold nanoparticle (AuNP)
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Citrylglutamate synthase deficient male mice are subfertile with impaired histone and transition protein 2 removal in late spermatids. Biochem. J. (IF 3.766) Pub Date : 2022-05-13 Lihua Wang-Eckhardt,Marc Sylvester,Ivonne Becker,Jean-Pierre Allam,Matthias Eckhardt
Chromatin remodelling in spermatids is an essential step in spermiogenesis and involves the exchange of most histones by protamines, which drives chromatin condensation in late spermatids. The gene Rimklb encodes a citrylglutamate synthase highly expressed in testes of vertebrates and the increase of its reaction product, β-citrylglutamate, correlates in time with the appearance of spermatids. Here
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Activation and manipulation of inflammasomes and pyroptosis during bacterial infections. Biochem. J. (IF 3.766) Pub Date : 2022-04-14 Elliott M Bernard,Petr Broz
Following detection of pathogen infection and disrupted cellular homeostasis, cells can activate a range of cell death pathways, such as apoptosis, necroptosis and pyroptosis, as part of their defence strategy. The initiation of pro-inflammatory, lytic pyroptosis is controlled by inflammasomes, which respond to a range of cellular perturbations. As is true for many host defence pathways, pathogens
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Ferroptosis in plants: regulation of lipid peroxidation and redox status. Biochem. J. (IF 3.766) Pub Date : 2022-04-14 Ayelén Mariana Distéfano,Gabriel Alejandro López,Victoria Bauer,Eduardo Zabaleta,Gabriela Carolina Pagnussat
Regulated cell death (RCD) is an essential process that plays key roles along the plant life cycle. Unlike accidental cell death, which is an uncontrolled biological process, RCD involves integrated signaling cascades and precise molecular-mediated mechanisms that are triggered in response to specific exogenous or endogenous stimuli. Ferroptosis is a cell death pathway characterized by the iron-dependent
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Allosteric pluripotency: challenges and opportunities Biochem. J. (IF 3.766) Pub Date : 2022-04-14 Akimoto, Madoka, Martinez Pomier, Karla, VanSchouwen, Bryan, Byun, Jung Ah, Khamina, Mariia, Melacini, Giuseppe
Allosteric pluripotency arises when the functional response of an allosteric receptor to an allosteric stimulus depends on additional allosteric modulators. Here, we discuss allosteric pluripotency as observed in the prototypical Protein Kinase A (PKA) as well as in other signaling systems, from typical multidomain signaling proteins to bacterial enzymes. We identify key drivers of pluripotent allostery
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LMAN1–MCFD2 complex is a cargo receptor for the ER-Golgi transport of α1-antitrypsin Biochem. J. (IF 3.766) Pub Date : 2022-04-14 Zhang, Yuan, Zhu, Min, Zheng, Chunlei, Wei, Wei, Emmer, Brian T., Zhang, Bin
α1-antitrypsin (AAT) is a serine protease inhibitor synthesized in hepatocytes and protects the lung from damage by neutrophil elastase. AAT gene mutations result in AAT deficiency (AATD), which leads to lung and liver diseases. The AAT Z variant forms polymer within the endoplasmic reticulum (ER) of hepatocytes and results in reduction in AAT secretion and severe disease. Previous studies demonstrated