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Histone H3K4ac, as a marker of active transcription start sites and enhancers, plays roles in histone eviction and RNA transcription BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-02-27 Jin Kang, Yujin Kang, AeRi Kim
The lysine 4 of histone H3 (H3K4) can be methylated or acetylated into four states: H3K4me1, H3K4me2, H3K4me3, or H3K4ac. Unlike H3K4 methylation, the genome-wide distribution and functional roles of H3K4ac remain unclear. To understand the relationship of acetylation with methylation at H3K4 and to explore the roles of H3K4ac in the context of chromatin, we analyzed H3K4ac across the human genome
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LncRNA-mediated orchestrations of alternative splicing in the landscape of breast cancer BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-02-08 Samarth Kansara, Prajwali Sawant, Taranjeet Kaur, Manoj Garg, Amit Kumar Pandey
Alternative splicing (AS) is a fundamental post-transcriptional process in eukaryotes, enabling a single gene to generate diverse mRNA transcripts, thereby enhancing protein variability. This process involves the excision of introns and the joining of exons in pre-mRNA(s) to form mature mRNA. The resulting mature mRNAs exhibit various combinations of exons, contributing to functional diversity. Dysregulation
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An epitope-tagged Swd2 reveals the different requirements of Swd2 concentration in H3K4 methylation and viability BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-02-06 Junsoo Oh, Seho Kim, SangMyung Kim, Jueun Kim, Soojin Yeom, Jung-Shin Lee
Swd2/Cps35 is a common component of the COMPASS H3K4 methyltransferase and CPF transcription termination complex in . The deletion of is lethal, which results from transcription termination defects in snoRNA genes. This study isolated a yeast strain that showed significantly reduced protein level of Swd2 following epitope tagging at its N-terminus (). The reduced level of Swd2 in the strain was insufficient
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Histone H2B ubiquitylation: Connections to transcription and effects on chromatin structure BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-02-06 Tasniem Fetian, Aakash Grover, Karen M. Arndt
Nucleosomes are major determinants of eukaryotic genome organization and regulation. Many studies, incorporating a diversity of experimental approaches, have been focused on identifying and discerning the contributions of histone post-translational modifications to DNA-centered processes. Among these, monoubiquitylation of H2B (H2Bub) on K120 in humans or K123 in budding yeast is a critical histone
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Targeting ‘histone mark’: Advanced approaches in epigenetic regulation of telomere dynamics in cancer BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-01-17 Ankita Das, Ashok K. Giri, Pritha Bhattacharjee
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Post-translational regulation of the mTORC1 pathway: A switch that regulates metabolism-related gene expression BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-01-18 Yitao Wang, Tobias Engel, Xinchen Teng
The mechanistic target of rapamycin complex 1 (mTORC1) is a kinase complex that plays a crucial role in coordinating cell growth in response to various signals, including amino acids, growth factors, oxygen, and ATP. Activation of mTORC1 promotes cell growth and anabolism, while its suppression leads to catabolism and inhibition of cell growth, enabling cells to withstand nutrient scarcity and stress
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Influence of cell volume on the gene transcription rate BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-01-19 José E. Pérez-Ortín, María J. García-Marcelo, Irene Delgado-Román, María C. Muñoz-Centeno, Sebastián Chávez
Cells vary in volume throughout their life cycle and in many other circumstances, while their genome remains identical. Hence, the RNA production factory must adapt to changing needs, while maintaining the same production lines. This paradox is resolved by different mechanisms in distinct cells and circumstances. RNA polymerases have evolved to cope with the particular circumstances of each case and
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Prospects and challenges of noncoding-RNA-mediated inhibition of heat shock protein 90 for cancer therapy BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2024-01-11 Shria Mattoo, Abha Gupta, Manvee Chauhan, Akshi Agrawal, Subrata Kumar Pore
Heat Shock Protein 90 (HSP90) is a potential drug target for cancer therapy as it is often dysregulated in several cancers, including lung, breast, pancreatic, and prostate cancers. In cancer, HSP90 fails to maintain the structural and functional integrity of its several client proteins which are involved in the hallmarks of cancer such as cell proliferation, invasion, migration, angiogenesis, and
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Insight into the mechanism of AML del(9q) progression: hnRNP K targets the myeloid master regulators CEBPA (C/EBPα) and SPI1 (PU.1) BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-11-25 Kerstin Rahn, Ali T. Abdallah, Lin Gan, Shelley Herbrich, Roland Sonntag, Oscar Benitez, Prerna Malaney, Xiaorui Zhang, Ashely G. Rodriguez, Jared Brottem, Gernot Marx, Tim H. Brümmendorf, Dirk H. Ostareck, Antje Ostareck-Lederer, Martina Crysandt, Sean M. Post, Isabel S. Naarmann-de Vries
Deletions on the long arm of chromosome 9 (del(9q)) are recurrent abnormalities in about 2 % of acute myeloid leukemia cases, which usually involve HNRNPK and are frequently associated with other known aberrations. Based on an Hnrnpk haploinsufficient mouse model, a recent study demonstrated a function of hnRNP K in pathogenesis of myeloid malignancies via the regulation of cellular proliferation and
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Modulation of Krüppel-like factors (KLFs) interaction with their binding partners in cancers through acetylation and phosphorylation BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-11-20 Kanupriya Jha, Amit Kumar, Kartik Bhatnagar, Anupam Patra, Neel Sarovar Bhavesh, Bipin Singh, Sarika Chaudhary
Post-translational modifications (PTMs) of transcription factors regulate transcriptional activity and play a key role in essentially all biological processes and generate indispensable insight towards biological function including activity state, subcellular localization, protein solubility, protein folding, substrate trafficking, and protein-protein interactions. Amino acids modified chemically via
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The association of the RSC remodeler complex with chromatin is influenced by the prefoldin-like Bud27 and determines nucleosome positioning and polyadenylation sites usage in Saccharomyces cerevisiae BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-11-13 Abel Cuevas-Bermúdez, Verónica Martínez-Fernández, Ana I. Garrido-Godino, Antonio Jordán-Pla, Xenia Peñate, Manuel Martín-Expósito, Gabriel Gutiérrez, Chhabi K. Govind, Sebastián Chávez, Vicent Pelechano, Francisco Navarro
The tripartite interaction between the chromatin remodeler complex RSC, RNA polymerase subunit Rpb5 and prefoldin-like Bud27 is necessary for proper RNA pol II elongation. Indeed lack of Bud27 alters this association and affects transcription elongation. This work investigates the consequences of lack of Bud27 on the chromatin association of RSC and RNA pol II, and on nucleosome positioning. Our results
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Isolation and characterisation of promoters from mouse genome to drive post-meiotic germ cell-specific robust gene expression for functional genomics studies BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-11-11 Abhishek Das, Srimoyee Koner, Subeer S. Majumdar, Nirmalya Ganguli
The generation of spermatozoa from developing germ cells through mitotic and meiotic divisions is a highly regulated and complex process. Any defect in this process, may lead to subfertility/infertility. The role of different transcripts (mRNA/miRNA/lncRNA) in regulation of the pre-meiotic, meiotic, and post-meiotic stages of spermatogenesis are being proposed based on various multiomics based approaches
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A poly-histidine motif of HOXA1 is involved in regulatory interactions with cysteine-rich proteins BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-11-11 Damien Marchese, Florent Guislain, Tamara Pringels, Laure Bridoux, René Rezsohazy
Homopolymeric amino acid repeats are found in about 24 % of human proteins and are over-represented in transcriptions factors and kinases. Although relatively rare, homopolymeric histidine repeats (polyH) are more significantly found in proteins involved in the regulation of embryonic development. To gain a better understanding of the role of polyH in these proteins, we used a bioinformatic approach
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The functions of FOXP transcription factors and their regulation by post-translational modifications BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-10-04 Congwen Gao, Honglin Zhu, Peng Gong, Chen Wu, Xingzhi Xu, Xuefei Zhu
The forkhead box subfamily P (FOXP) of transcription factors, consisting of FOXP1, FOXP2, FOXP3, and FOXP4, is involved in the regulation of multisystemic functioning. Disruption of the transcriptional activity of FOXP proteins leads to neurodevelopmental disorders and immunological diseases, as well as the suppression or promotion of carcinogenesis. The transcriptional activities of FOXP proteins
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DDX5 (p68) orchestrates β-catenin, RelA and SP1 mediated MGMT gene expression in human colon cancer cells: Implication in TMZ chemoresistance BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-10-02 Rajni Shaw, Subhajit Karmakar, Malini Basu, Mrinal K. Ghosh
DDX5 (p68) upregulation has been linked with various cancers of different origins, especially Colon Adenocarcinomas. Similarly, across cancers, MGMT has been identified as the major contributor of chemoresistance against DNA alkylating agents like Temozolomide (TMZ). TMZ is an emerging potent chemotherapeutic agent across cancers under the arena of drug repurposing. Recent studies have established
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Post-translational modifications in stress granule and their implications in neurodegenerative diseases BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-24 Zhangshun Wang, Chen'ang Zhang, Chenyu Fan, Yanfen Liu
Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins
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Inflammation-induced nitric oxide suppresses PPARα expression and function via downregulation of Sp1 transcriptional activity in adipocytes BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-20 Jungin Kwon, Yumeko Aoki, Haruya Takahashi, Rieko Nakata, Satoko Kawarasaki, Zheng Ni, Rina Yu, Hiroyasu Inoue, Kazuo Inoue, Teruo Kawada, Tsuyoshi Goto
The activation of peroxisome proliferator-activated receptor alpha (PPARα), a ligand-dependent transcription factor that regulates lipid oxidation-related genes, has been employed to treat hyperlipidemia. Emerging evidence indicates that Ppara gene expression decreases in adipose tissue under obese conditions; however, the underlying molecular mechanisms remain elusive. Here, we demonstrate that nitric
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Entanglement of MAPK pathways with gene expression and its omnipresence in the etiology for cancer and neurodegenerative disorders BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-21 Joydeep Chakraborty, Sayan Chakraborty, Sohag Chakraborty, Mahesh N. Narayan
Mitogen Activated Protein Kinase (MAPK) is one of the most well characterized cellular signaling pathways that controls fundamental cellular processes including proliferation, differentiation, and apoptosis. These cellular functions are consequences of transcription of regulatory genes that are influenced and regulated by the MAP-Kinase signaling cascade. MAP kinase components such as Receptor Tyrosine
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Unraveling the battle for lysine: A review of the competition among post-translational modifications BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-24 Ali H. Shukri, Valentina Lukinović, François Charih, Kyle K. Biggar
Proteins play a critical role as key regulators in various biological systems, influencing crucial processes such as gene expression, cell cycle progression, and cellular proliferation. However, the functions of proteins can be further modified through post-translational modifications (PTMs), which expand their roles and contribute to disease progression when dysregulated. In this review, we delve
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The mechanism of UP1 binding and unfolding of human telomeric DNA G-quadruplex BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-16 Xiaobin Ling, Yuqi Yao, Lei Ding, Jinbiao Ma
The human telomere contains multiple copies of the DNA sequence d(TTAGGG) which can fold into higher order intramolecular G-quadruplexes and regulate the maintenance of telomere length and chromosomal integrity. The nucleic acid binding protein heteronuclear ribonucleoprotein A1 (hnRNP A1) and its N-terminus proteolytic product UP1 have been shown to efficiently bind and unfold telomeric DNA G-quadruplex
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Post translational modifications at the verge of plant-geminivirus interaction BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-17 Ashish Prasad, Shambhavi Sharma, Manoj Prasad
Plant-virus interaction is a complex phenomenon and involves the communication between plant and viral factors. Viruses have very limited coding ability yet, they are able to cause infection which results in huge agro-economic losses throughout the globe each year. Post-translational modifications (PTMs) are covalent modifications of proteins that have a drastic effect on their conformation, stability
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Regulation of SARS-CoV-2 infection and antiviral innate immunity by ubiquitination and ubiquitin-like conjugation BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-17 Yi Zheng, Huiyu Yang, Xuejing Zhang, Chengjiang Gao
A global pandemic COVID-19 resulting from SARS-CoV-2 has affected a significant portion of the human population. Antiviral innate immunity is critical for controlling and eliminating the viral infection. Ubiquitination is extensively involved in antiviral signaling, and recent studies suggest that ubiquitin-like proteins (Ubls) modifications also participate in innate antiviral pathways such as RLR
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KDM5A noncanonically binds antagonists MLL1/2 to mediate gene regulation and promotes epithelial to mesenchymal transition BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-16 R. Kirtana, Soumen Manna, Samir Kumar Patra
Differential expression of genes involved in certain processes is a collaborative outcome of crosstalk between signalling molecules and epigenetic modifiers. In response to environmental stimulus, interplay between transcription factors and epigenetic modifiers together dictates the regulation of genes. MLLs and KDM5A are functionally antagonistic proteins, as one acts as a writer and the other erases
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The presence of an intron relieves gene repression caused by promoter-proximal four-bp specific sequences in yeast BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-09-01 Hiroki Kikuta, Takahiro Aramaki, Shingo Mabu, Rinji Akada, Hisashi Hoshida
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UPS writes a new saga of SAGA BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-30 Priyanka Barman, Pritam Chakraborty, Rhea Bhaumik, Sukesh R. Bhaumik
SAGA (Spt-Ada-Gcn5-Acetyltransferase), an evolutionarily conserved transcriptional co-activator among eukaryotes, is a large multi-subunit protein complex with two distinct enzymatic activities, namely HAT (Histone acetyltransferase) and DUB (De-ubiquitinase), and is targeted to the promoter by the gene-specific activator proteins for histone covalent modifications and PIC (Pre-initiation complex)
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The versatility of the proteasome in gene expression and silencing: Unraveling proteolytic and non-proteolytic functions BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-24 Hyesu Lee, Sungwook Kim, Daeyoup Lee
The 26S proteasome consists of a 20S core particle and a 19S regulatory particle and critically regulates gene expression and silencing through both proteolytic and non-proteolytic functions. The 20S core particle mediates proteolysis, while the 19S regulatory particle performs non-proteolytic functions. The proteasome plays a role in regulating gene expression in euchromatin by modifying histones
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Role of clusterin gene 3’-UTR polymorphisms and promoter hypomethylation in the pathogenesis of pseudoexfoliation syndrome and pseudoexfoliation glaucoma BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-29 Ramani Shyam Kapuganti, Lipsa Sahoo, Pranjya Paramita Mohanty, Bushra Hayat, Sucheta Parija, Debasmita Pankaj Alone
Pseudoexfoliation (PEX) is a multifactorial age-related disease characterized by the deposition of extracellular fibrillar aggregates in the anterior ocular tissues. This study aims to identify the genetic and epigenetic contribution of clusterin (CLU) in PEX pathology. CLU is a molecular chaperone upregulated in PEX and genetically associated with the disease. Sequencing of a 2.9 kb region encompassing
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Ubiquitination and deubiquitination: Implications on cancer therapy BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-24 Gunjan Dagar, Rakesh Kumar, Kamlesh K. Yadav, Mayank Singh, Tej K. Pandita
The ubiquitin proteasomal system (UPS) represents a highly regulated protein degradation pathway essential for maintaining cellular homeostasis. This system plays a critical role in several cellular processes, which include DNA damage repair, cell cycle checkpoint control, and immune response regulation. Recently, the UPS has emerged as a promising target for cancer therapeutics due to its involvement
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Protein post-translational modifications: A key factor in colorectal cancer resistance mechanisms BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-23 Bo Bi, Miaojuan Qiu, Peng Liu, Qiang Wang, Yingfei Wen, You Li, Binbin Li, Yongshu Li, Yulong He, Jing Zhao
Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Despite advances in treatment, drug resistance remains a critical impediment. Post-translational modifications (PTMs) regulate protein stability, localization, and activity, impacting vital cellular processes. Recent research has highlighted the essential role of PTMs in the development of CRC resistance. This review summarizes
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Post-translational modifications of lysine-specific demethylase 1 BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-10 Dongha Kim, Hye Jin Nam, Sung Hee Baek
Lysine-specific demethylase 1 (LSD1) is crucial for regulating gene expression by catalyzing the demethylation of mono- and di-methylated histone H3 lysine 4 (H3K4) and lysine 9 (H3K9) and non-histone proteins through the amine oxidase activity with FAD+ as a cofactor. It interacts with several protein partners, which potentially contributes to its diverse substrate specificity. Given its pivotal role
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N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-06 Yuting Sun, De Jin, Ziwei Zhang, Hangyu Ji, Xuedong An, Yuehong Zhang, Cunqing Yang, Wenjie Sun, Yuqing Zhang, Yingying Duan, Xiaomin Kang, Linlin Jiang, Xuefei Zhao, Fengmei Lian
The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as “writers,” and demethylases, known as “erasers,” leading to a dynamic and reversible process. Changes in m6A levels have been implicated in a wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, and RNA splicing, establishing a strong correlation with various
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Effect of CDK7 inhibitor on MYCN-amplified retinoblastoma BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-08-01 Hanyue Xu, Lirong Xiao, Yi Chen, Yilin Liu, Yifan Zhang, Yuzhu Gao, Shulei Man, Naihong Yan, Ming Zhang
Retinoblastoma (RB) is a common malignancy that primarily affects pediatric populations. Although a well-known cause of RB is RB1 mutation, MYCN amplification can also lead to the disease, which is a poor prognosis factor. Studies conducted in various tumor types have shown that MYCN inhibition is an effective approach to impede tumor growth. Various indirect approaches have been developed to overcome
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Dynamics of epigenetic control in plants via SET domain containing proteins: Structural and functional insights BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-31 Sushmita Seni, Roshan Kumar Singh, Manoj Prasad
Plants control expression of their genes in a way that involves manipulating the chromatin structural dynamics in order to adapt to environmental changes and carry out developmental processes. Histone modifications like histone methylation are significant epigenetic marks which profoundly and globally modify chromatin, potentially affecting the expression of several genes. Methylation of histones is
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ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-30 Shuxiang Chen, Xiaotong Zhu, Wenhuan Ou, Le Kang, Jian Situ, Zhipeng Liao, Li Huang, Weizhong Qi, Songjia Ni
Osteoarthritis (OA) is the most common irreversible chronic joint dysfunction disease, which is pathologically characterized by disturbance of articular cartilage homeostasis leading to subsequent inflammatory response and cartilage extracellular matrix (ECM) degradation. Increasing evidence has demonstrated the dysregulation of transcription factors play crucial roles in the occurrence and development
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Crystal structure of Tudor domain of TDRD3 in complex with a small molecule antagonist BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-25 Meixia Chen, Zhuowen Wang, Weiguo Li, Yichang Chen, Qin Xiao, Xinci Shang, Xiaolei Huang, Zhengguo Wei, Xinyue Ji, Yanli Liu
Tudor domain-containing protein 3 (TDRD3) is involved in regulating transcription and translation, promoting breast cancer progression, and modulating neurodevelopment and mental health, making it a promising therapeutic target for associated diseases. The Tudor domain of TDRD3 is essential for its biological functions, and targeting this domain with potent and selective chemical probes may modulate
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Differences and similarities in recognition of co-factors by Taf14 BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-22 Minh Chau Nguyen, Duo Wang, Brianna J. Klein, Yong Chen, Tatiana G. Kutateladze
Taf14 is a subunit of multiple fundamental complexes implicated in transcriptional regulation and DNA damage repair in yeast cells. Here, we investigate the association of Taf14 with the consensus sequence present in other subunits of these complexes and describe the mechanistic features that affect this association. We demonstrate that the precise molecular mechanisms and biological outcomes underlying
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Multimerization of HIF enhances transcription of target genes containing the hypoxia ancillary sequence BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-25 Tamara Rosell-Garcia, Sergio Rivas-Muñoz, Koryu Kin, Verónica Romero-Albillo, Silvia Alcaraz, Carlos Fernandez-Tornero, Fernando Rodriguez-Pascual
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PP2A and its adapter protein IER5 induce the DNA-binding ability and target gene expression of E2F1 via dephosphorylation at serine 375 BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-17
The transcription factor E2F1 participates in cell cycle control through transcriptional activation of genes that promote S-phase entry. E2F1 is also linked to the expression of proapoptotic genes, and the loss of E2F1 activity facilitates tumor progression by reducing cellular apoptosis. Phosphorylation controlled by protein kinases and phosphatases is the major posttranslational modification and
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The yeast mRNA-binding protein Cth2 post-transcriptionally modulates ergosterol biosynthesis in response to iron deficiency BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-14
Sterol synthesis is an iron-dependent metabolic pathway in eukaryotes. Consequently, fungal ergosterol biosynthesis (ERG) is down-regulated in response to iron deficiency. In this report, we show that, upon iron limitation or overexpression of the iron-regulated mRNA-binding protein Cth2, the yeast Saccharomyces cerevisiae down-regulates the three initial enzymatic steps of ergosterol synthesis (ERG1
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The fine-tuned crosstalk between lysine acetylation and the circadian rhythm BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-07-13 Honglv Jiang, Xiaohui Wang, Jingjing Ma, Guoqiang Xu
Circadian rhythm is a roughly 24-h wake and sleep cycle that almost all of the organisms on the earth follow when they execute their biological functions and physiological activities. The circadian clock is mainly regulated by the transcription-translation feedback loop (TTFL), consisting of the core clock proteins, including BMAL1, CLOCK, PERs, CRYs, and a series of accessory factors. The circadian
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A novel endoplasmic reticulum adaptation is critical for the long-lived Caenorhabditis elegans rpn-10 proteasomal mutant BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-06-22 Meghna N. Chinchankar, William B. Taylor, Su-Hyuk Ko, Ellen C. Apple, Karl A. Rodriguez, Lizhen Chen, Alfred L. Fisher
The loss of proteostasis due to reduced efficiency of protein degradation pathways plays a key role in multiple age-related diseases and is a hallmark of the aging process. Paradoxically, we have previously reported that the Caenorhabditis elegans rpn-10(ok1865) mutant, which lacks the RPN-10/RPN10/PSMD4 subunit of the 19S regulatory particle of the 26S proteasome, exhibits enhanced cytosolic proteostasis
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New roles for elongation factors in RNA polymerase II ubiquitylation and degradation BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-06-17 Joseph C. Reese
RNA polymerase II (RNAPII) encounters numerous impediments on its way to completing mRNA synthesis across a gene. Paused and arrested RNAPII are reactivated or rescued by elongation factors that travel with polymerase as it transcribes DNA. However, when RNAPII fails to resume transcription, such as when it encounters an unrepairable bulky DNA lesion, it is removed by the targeting of its largest subunit
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Ubiquitination is a major modulator for the activation of inflammasomes and pyroptosis BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-06-17 Qiuyun Jiang, Zhigang Zhu, Xinliang Mao
Inflammasomes are a central node of the innate immune defense system against the threat of homeostatic perturbance caused by pathogenic organisms or host-derived molecules. Inflammasomes are generally composed of multimeric protein complexes that assemble in the cytosol after sensing danger signals. Activated inflammasomes promote downstream proteolytic activation, which triggers the release of pro-inflammatory
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TRIM25-mediated ubiquitination of G3BP1 regulates the proliferation and migration of human neuroblastoma cells BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-06-10 Yun Yang, Yanyan Luo, Cong Yang, Ronggui Hu, Xiong Qin, Chuanyin Li
Neuroblastoma is one of the most severe malignant tumors and accounts for substantial cancer-related mortality in children. Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is highly expressed in various cancers and acts as an important biomarker of poor prognosis. The ablation of G3BP1 inhibited the proliferation and migration of human SHSY5Y cells. Because of its important role
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Quantitative proteomics revealed the transition of ergosterol biosynthesis and drug transporters processes during the development of fungal fluconazole resistance BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-06-10 Xinying Sui, Xinyu Cheng, Zhaodi Li, Yonghong Wang, Zhenpeng Zhang, Ruyue Yan, Lei Chang, Yanchang Li, Ping Xu, Changzhu Duan
Fungal infections and antifungal resistance are the increasing global public health concerns. Mechanisms of fungal resistance include alterations in drug-target interactions, detoxification by high expression of drug efflux transporters, and permeability barriers associated with biofilms. However, the systematic panorama and dynamic changes of the relevant biological processes of fungal drug resistance
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N/C-degron pathways and inhibitor development for PROTAC applications BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-05-30 Zhibin Wu, Yunyuan Huang, Ke Liu, Jinrong Min
Ubiquitination is a fascinating post-translational modification that has received continuous attention since its discovery. In this review, we first provide a concise overview of the E3 ubiquitin ligases, delving into classification, characteristics and mechanisms of ubiquitination. We then specifically examine the ubiquitination pathways mediated by the N/C-degrons, discussing their unique features
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Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-05-20 Laura Vanagas, Daniela Muñoz, Constanza Cristaldi, Agustina Ganuza, Rosario Nájera, Mabel C. Bonardi, Valeria R. Turowski, Fanny Guzman, Bin Deng, Kami Kim, William J. Sullivan, Sergio O. Angel
Through regulation of DNA packaging, histone proteins are fundamental to a wide array of biological processes. A variety of post-translational modifications (PTMs), including acetylation, constitute a proposed histone code that is interpreted by “reader” proteins to modulate chromatin structure. Canonical histones can be replaced with variant versions that add an additional layer of regulatory complexity
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Fine tuning of the transcription juggernaut: A sweet and sour saga of acetylation and ubiquitination BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-05-24 Avik Ghosh, Poushali Chakraborty, Debabrata Biswas
Among post-translational modifications of proteins, acetylation, phosphorylation, and ubiquitination are most extensively studied over the last several decades. Owing to their different target residues for modifications, cross-talk between phosphorylation with that of acetylation and ubiquitination is relatively less pronounced. However, since canonical acetylation and ubiquitination happen only on
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Allelic variation within the major APOE CpG island affects its methylation in the brain of targeted replacement mice expressing human APOE BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-05-15 Johanna Rueter, Gerald Rimbach, Patricia Huebbe
• The number of cytosine-phosphate-guanine (CpG) sites differs due to sequence variation in the human apolipoprotein E (APOE) gene. • APOE DNA methylation is allele-dependently altered corresponding to the total number of CpG pairs in the brain of APOE targeted replacement mice (APOE εpsilon 4 > εpsilon 3 > εpsilon 2). • Binding of the methyl-CpG binding protein 2 to genomic APOE was in trend less
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Sirtuin4 impacts mitochondrial homeostasis in pancreatic cancer cells by reducing the stability of AlkB homolog 1 via deacetylation of the HRD1-SEL1L complex BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-05-03 Dongnan Ping, Xiaofan Pu, Guoping Ding, Chaolei Zhang, Junbin Jin, Chengjie Xu, Jiazheng Liu, Shengnan Jia, Liping Cao
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DNA-PKcs as an upstream mediator of OCT4-induced MYC activation in small cell lung cancer BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-26 Sung-Jen Wei, In-Hyoung Yang, Ismail S. Mohiuddin, Ganesh J. Kshirsagar, Thinh H. Nguyen, Scott Trasti, Barry J. Maurer, Min H. Kang
Small cell lung cancer (SCLC) is a neuroendocrine tumor noted for the rapid development of both metastases and resistance to chemotherapy. High mutation burden, ubiquitous loss of TP53 and RB1, and a mutually exclusive amplification of MYC gene family members contribute to genomic instability and make the development of new targeted agents a challenge. Previously, we reported a novel OCT4-induced MYC
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Proteomic approaches to study ubiquitinomics BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-29 Indrajit Sahu, He Zhu, Sara J. Buhrlage, Jarrod A. Marto
As originally described some 40 years ago, protein ubiquitination was thought to serve primarily as a static mark for protein degradation. In the ensuing years, it has become clear that ‘ubiquitination’ is a structurally diverse and dynamic post-translational modification and is intricately involved in a myriad of signaling pathways in all eukaryote cells. And like other key pathways in the functional
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“MiR-7 controls cholesterol biosynthesis through posttranscriptional regulation of DHCR24 expression” BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-21 Mario Fernández-de Frutos, Virginia Pardo-Marqués, Marta Torrecilla-Parra, Patricia Rada, Ana Pérez-García, Yolanda Martín-Martín, Gema de la Peña, Ana Gómez, Ana Toledano-Zaragoza, Diego Gómez-Coronado, María José Casarejos, José M. Solís, Noemí Rotllan, Óscar Pastor, María Dolores Ledesma, Ángela M. Valverde, Rebeca Busto, Cristina M. Ramírez
Dysregulation of cholesterol homeostasis is associated with several pathologies including cardiovascular diseases and neurological disorders such as Alzheimer's disease (AD). MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of cholesterol metabolism. We previously established the role of miR-7 in regulating insulin resistance and amyloidosis, which represents a common pathological
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UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-19 Xianyan Hu, Rong Zou, Zaihui Zhang, Jia Ji, Jiqiang Li, Xin-Yu Huo, Di Liu, Man-Xi Ge, Meng-Ke Cui, Ming-Zhi Wu, Zhao-Peng Li, Qingchen Wang, Xiaoli Zhang, Zai-Rong Zhang
The transcription factor nuclear factor erythroid 2 like 1 (NFE2L1 or NRF1) regulates constitutive and inducible expression of proteasome subunits and assembly chaperones. The precursor of NRF1 is integrated into the endoplasmic reticulum (ER) and can be retrotranslocated from the ER to the cytosol where it is processed by ubiquitin-directed endoprotease DDI2. DDI2 cleaves and activates NRF1 only when
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Alzheimer's disease-associated mutant ubiquitin (UBB+1) is secreted through an autophagosome-like vesicle-mediated unconventional pathway BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-17 Ajay R. Wagh, Prasad Sulakshane, Michael H. Glickman
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Iron restriction increases the expression of a cytotoxic cysteine proteinase TvCP2 by a novel mechanism of tvcp2 mRNA alternative polyadenylation in Trichomonas vaginalis BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-02 Luis Alberto Rivera-Rivas, Rossana Arroyo
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The DEAD-box RNA helicase DDX5 (p68) and β-catenin: The crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-03-29 Shaheda Tabassum, Malini Basu, Mrinal K. Ghosh
Forkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. DDX5 (p68), an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating
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Post-translational regulation of proto-oncogene ZBTB7A expression by p53 status in cancer cells: HSP90-dependent stabilization vs. p53-KLHL20-ubiquitin proteasomal degradation BBA Gene Regul. Mech. (IF 4.7) Pub Date : 2023-04-01 Seo-Hyun Choi, Su-Yeon Cho, Sun Young Park, Man-Wook Hur
ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells. Interestingly, inhibition of HSP90 decreased ZBTB7A expression