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  • Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-04-06
    Shuling Song; Eric W.-F. Lam; Tamara Tchkonia; James L. Kirkland; Yu Sun

    Aging is a major risk factor for numerous human pathologies, including cardiovascular, metabolic, musculoskeletal, and neurodegenerative conditions and various malignancies. While our understanding of aging is far from complete, recent advances suggest that targeting fundamental aging processes can delay, prevent, or alleviate age-related disorders. Cellular senescence is physiologically beneficial

    更新日期:2020-04-06
  • Natural Compounds as Pharmaceuticals: The Key Role of Cytochromes P450 Reactivity
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-04-05
    Giovanna Di Nardo; Gianfranco Gilardi

    The design of drugs from natural products is a re-emerging area due to the need for bioactive compounds. The exploitation of natural products and their derivatives obtained by biocatalysis is in line with the higher attention given today to new sustainable technologies that better preserve the environment (green chemistry). The research field of cytochromes P450 (CYPs) is continuously providing new

    更新日期:2020-04-06
  • Global Approaches in Studying RNA-Binding Protein Interaction Networks
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-04-02
    Erin L. Sternburg; Fedor V. Karginov

    RNA-binding proteins (RBPs) play crucial roles in almost all aspects of cellular biology. RBP binding at specific target sites impacts expression of functionally coordinated sets of mRNAs and involves combinatorial and dynamic interactions with other RBPs. The complexity and principles of these regulatory networks are only beginning to be understood. In recent years, transcriptome-wide experimental

    更新日期:2020-04-03
  • Mimicry of Short Linear Motifs by Bacterial Pathogens: A Drugging Opportunity
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-30
    Hugo Sámano-Sánchez; Toby J. Gibson

    Bacterial pathogens have developed complex strategies to successfully survive and proliferate within their hosts. Throughout the infection cycle, direct interaction with host cells occurs. Many bacteria have been found to secrete proteins, such as effectors and toxins, directly into the host cell with the potential to interfere with cell regulatory processes, either enzymatically or through protein–protein

    更新日期:2020-03-30
  • Toward Organism-scale Structural Biology: S-layer Reined in by Bacterial LPS
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-27
    Morgan Beeby

    Technical developments are unifying molecular and cellular biology. A recent electron cryotomography study by von Kügelgen et al. highlights the bright future for such studies, seamlessly integrating near-atomic resolution protein structures, organism-scale architecture, native mass spectrometry, and molecular dynamic simulations to clarify how the Caulobacter crescentus S-layer assembles on the lipopolysaccharides

    更新日期:2020-03-27
  • Art and Science of the Cellular Mesoscale
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-21
    David S. Goodsell; Arthur J. Olson; Stefano Forli

    Experimental information from microscopy, structural biology, and bioinformatics may be integrated to build structural models of entire cells with molecular detail. This integrative modeling is challenging in several ways: the intrinsic complexity of biology results in models with many closely packed and heterogeneous components; the wealth of available experimental data is scattered among multiple

    更新日期:2020-03-21
  • Phytochemicals as Prebiotics and Biological Stress Inducers
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-17
    Jan Martel; David M. Ojcius; Yun-Fei Ko; John D. Young

    Phytochemicals in fruits and vegetables produce health benefits, but questions remain regarding their bioavailability, molecular targets, and mechanism of action. Here, we address these issues by considering the prebiotic and biological properties of phytochemicals. A fraction of phytochemicals consumed orally passes through the gut lumen, where it modulates the composition of the gut microbiota and

    更新日期:2020-03-19
  • SAGA Structures Provide Mechanistic Models for Gene Activation
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-16
    Jelly H.M. Soffers; Varvara V. Popova; Jerry L.W. Workman

    Two recent reports by Cramer and Ben-Shem and colleagues present high-resolution structures of the yeast SAGA transcription coactivator complex. These are the first to resolve the stoichiometry and structure of the core. The core contains an octamer-like fold, flexibly links the enzymatic modules, and facilitates TBP loading onto TATA promoters.

    更新日期:2020-03-16
  • Gene-Specific Actions of Transcriptional Coregulators Facilitate Physiological Plasticity: Evidence for a Physiological Coregulator Code
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-13
    Michael R. Stallcup; Coralie Poulard

    The actions of transcriptional coregulators are highly gene-specific, that is, each coregulator is required only for a subset of the genes regulated by a specific transcription factor. These coregulator-specific gene subsets often represent selected physiological responses among multiple pathways targeted by a transcription factor. Regulating the activity of a coregulator via post-translational modifications

    更新日期:2020-03-16
  • Binge Drinking: Macropinocytosis Promotes Tumorigenic Growth of RAS-Mutant Cancers
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-09
    G. Aaron Hobbs; Channing J. Der

    The RAS oncoprotein drives elevated macropinocytosis, a metabolic process essential for cancer growth. A recent study by Ramirez et al. elucidated a mechanism whereby RAS controls V-ATPase association with the plasma membrane to drive RAC1 GTPase-dependent macropinocytosis. Potentially actionable targets to disrupt this RAS-dependent nutrient acquisition pathway were identified.

    更新日期:2020-03-10
  • Outlining the Complex Pathway of Mammalian Fe-S Cluster Biogenesis
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-06
    Nunziata Maio; Tracey A. Rouault

    Iron–sulfur (Fe-S) clusters (ISCs) are ubiquitous cofactors essential to numerous fundamental cellular processes. Assembly of ISCs and their insertion into apoproteins involves the function of complex cellular machineries that operate in parallel in the mitochondrial and cytosolic/nuclear compartments of mammalian cells. The spectrum of diseases caused by inherited defects in genes that encode the

    更新日期:2020-03-06
  • Activation and Regulation of Cytoplasmic Dynein
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-05
    John T. Canty; Ahmet Yildiz

    Cytoplasmic dynein is an AAA+ motor that drives the transport of many intracellular cargoes towards the minus end of microtubules (MTs). Previous in vitro studies characterized isolated dynein as an exceptionally weak motor that moves slowly and diffuses on an MT. Recent studies altered this view by demonstrating that dynein remains in an autoinhibited conformation on its own, and processive motility

    更新日期:2020-03-05
  • Unfolded Protein Response (UPR) Controls Major Senescence Hallmarks
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-03-04
    Corinne Abbadie; Olivier Pluquet

    Senescence is a complex cellular state, which can be considered as a stress response phenotype. However, the mechanisms through which cells acquire and maintain this phenotype are not fully understood. In this paper, it is argued that the unfolded protein response (UPR) may represent a signalling platform that is associated with the major senescence hallmarks.

    更新日期:2020-03-05
  • Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-28
    Casey P. Nielsen; Jason A. MacGurn

    In eukaryotic cells, proteome remodeling is mediated by the ubiquitin–proteasome system, which regulates protein degradation, trafficking, and signaling events in the cell. Interplay between the cellular proteome and ubiquitin is complex and dynamic and many regulatory features that support this system have only recently come into focus. An unexpected recurring feature in this system is the physical

    更新日期:2020-02-28
  • Acquired ‘Phase Separation’ Underlies Aberrant Cell Fate Control?
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-27
    Yifei Gao; Pilong Li

    Chromatin readers are important intermediaries linking epigenetic information and biological phenotypes. Many diseases are caused by mutations in epigenetic readers. Recently, a study by Wan et al. uncovered that cancer-associated mutations promote self-association of eleven-nineteen-leukemia protein (ENL), leading to abnormal condensates, elevated gene expression, and impaired cell fate determination

    更新日期:2020-02-27
  • Structural Insights into the Activation of mTORC1 on the Lysosomal Surface
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-27
    Jin H. Park; Gina Lee; John Blenis

    Using cryo-electron microscopy and molecular characterization, David Sabatini and colleagues provide crucial new insights that validate and expand their model of how amino acids are sensed and signal at the lysosome to activate mechanistic target of rapamycin complex 1 (mTORC1) and cell growth-regulating processes. This work also reveals new therapeutic opportunities for mTORC1-driven diseases.

    更新日期:2020-02-27
  • Say Cheese: Structure of the Cardiac Electrical Engine Is Captured
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-24
    Mohammad-Reza Ghovanloo; Peter C. Ruben

    Voltage-gated sodium channel (Nav)1.5 is the predominantly expressed sodium channel in the myocardium. Mutations in the gene encoding Nav1.5 are associated with several types of cardiac arrhythmias. In their recent study, Jiang et al. provide a detailed structure of the rat Nav1.5, with major implications regarding its physiology, pharmacology, and pathophysiology.

    更新日期:2020-02-24
  • Emerging Features of Linear Motif-Binding Hub Proteins
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-20
    Nathan Jespersen; Elisar Barbar

    Hub proteins are important elements of interactomes within an organism; they bind diverse partners, display significant pleiotropy, and connect many cellular systems. Static hubs interact with their partners simultaneously, while dynamic hubs bind different partners at different locations and times. Although this distinguishes some features of hub protein/partner interactions, the increasing literature

    更新日期:2020-02-20
  • Mechanisms and Functions of Chromosome Compartmentalization
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-18
    Erica M. Hildebrand; Job Dekker

    Active and inactive chromatin are spatially separated in the nucleus. In Hi-C data, this is reflected by the formation of compartments, whose interactions form a characteristic checkerboard pattern in chromatin interaction maps. Only recently have the mechanisms that drive this separation come into view. Here, we discuss new insights into these mechanisms and possible functions in genome regulation

    更新日期:2020-02-20
  • Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-17
    Xiaofeng Qi; Xiaochun Li

    Cell differentiation and proliferation require Hedgehog (HH) signaling and aberrant HH signaling causes birth defects or cancers. In this signaling pathway, the N-terminally palmitoylated and C-terminally cholesterylated HH ligand is secreted into the extracellular space with help of the Dispatched-1 (DISP1) and Scube2 proteins. The Patched-1 (PTCH1) protein releases its inhibition of the oncoprotein

    更新日期:2020-02-20
  • The Structure of ASFV Advances the Fight against the Disease
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-17
    Yuejiao Xian; Chuan Xiao

    African swine fever virus (ASFV) is the causative pathogen of the recent African swine fever epidemic, with devastating impacts on economy. A recent study by Wang et al. reveals the multilayer structural details of ASFV at near-atomic resolution, which provides interesting insights about giant virus assembly and paves the way for vaccine development.

    更新日期:2020-02-20
  • STRIPAK Is a Regulatory Hub Initiating Hippo Signaling
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-15
    Amin Ardestani; Kathrin Maedler

    Signaling modules that integrate the diverse extra- and intracellular inputs to the Hippo pathway were previously unknown. By biochemical and molecular interrogation, Chen et al. established a molecular framework, the RhoA-RHPN-NF2/Kibra-STRIPAK axis, that regulates the status of Hippo core kinases and connects upstream signals to initiate and orchestrate the Hippo pathway.

    更新日期:2020-02-20
  • Nucleoporin Condensates Drive Nuclear Pore Complex Assembly in Oocytes
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-13
    George W. Mobbs; André Hoelz

    Oocytes stockpile nuclear pore complexes (NPCs) in cytoplasmic membrane sheets called annulate lamellae (AL) in preparation for rapid cell cycles during embryogenesis. Recently, Hampoelz et al. reported that AL–NPC assembly depends on the coordinated formation, transport, and interaction of biomolecular condensates containing distinct sets of nucleoporins.

    更新日期:2020-02-20
  • To Eat or to Die: Deciphering Selective Forms of Autophagy.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-07
    Alibek Abdrakhmanov,Vladimir Gogvadze,Boris Zhivotovsky

    Autophagy is an evolutionarily conserved process whereby damaged and redundant components of the cell are degraded in structures called autophagolysosomes. Currently, three main types of autophagy are recognized: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). However, we still know little about some specific types of autophagy that are linked to various intracellular compartments

    更新日期:2020-02-10
  • Proteomic Technologies for Deciphering Local and Global Protein Interactions.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-02-05
    Todd M Greco,Michelle A Kennedy,Ileana M Cristea

    更新日期:2020-02-05
  • Miniproteins as a Powerful Modality in Drug Development.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-31
    Zachary R Crook,Natalie W Nairn,James M Olson

    Miniproteins are a diverse group of protein scaffolds characterized by small (1-10 kDa) size, stability, and versatility in drug-like roles. Coming largely from native sources, they have been widely adopted into drug development pipelines. While their structures and capabilities are diverse, the approaches to their utilization share more similarities with each other than with more widely used modalities

    更新日期:2020-02-03
  • Learning of Signaling Networks: Molecular Mechanisms.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-30
    Péter Csermely,Nina Kunsic,Péter Mendik,Márk Kerestély,Teodóra Faragó,Dániel V Veres,Péter Tompa

    Molecular processes of neuronal learning have been well described. However, learning mechanisms of non-neuronal cells are not yet fully understood at the molecular level. Here, we discuss molecular mechanisms of cellular learning, including conformational memory of intrinsically disordered proteins (IDPs) and prions, signaling cascades, protein translocation, RNAs [miRNA and long noncoding RNA (lncRNA)]

    更新日期:2020-01-31
  • Structure and Roles of V-type ATPases.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-27
    Thamiya Vasanthakumar,John L Rubinstein

    V-ATPases are membrane-embedded protein complexes that function as ATP hydrolysis-driven proton pumps. V-ATPases are the primary source of organellar acidification in all eukaryotes, making them essential for many fundamental cellular processes. Enzymatic activity can be modulated by regulated and reversible disassembly of the complex, and several subunits of mammalian V-ATPase have multiple isoforms

    更新日期:2020-01-29
  • N-Terminal Proteoforms in Human Disease.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-27
    Annelies Bogaert,Esperanza Fernandez,Kris Gevaert

    The collection of chemically different protein variants, or proteoforms, by far exceeds the number of protein-coding genes in the human genome. Major contributors are alternative splicing and protein modifications. In this review, we focus on those proteoforms that differ at their N termini with a molecular link to disease. We describe the main underlying mechanisms that give rise to such N-terminal

    更新日期:2020-01-27
  • How Cells Respond to DNA Breaks in Mitosis.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-27
    Andrew N Blackford,Manuel Stucki

    DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to chromosomal instability if they are not repaired correctly. DSBs are especially dangerous in mitosis when cells go through the complex process of equal chromosome segregation into daughter cells. When cells encounter DSBs in interphase, they are able to arrest the cell cycle until the breaks are repaired before entering mitosis

    更新日期:2020-01-27
  • FANally…A Structure Emerges of the Fanconi Anemia Core Complex.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-24
    Jacob D Aguirre,Nicolas H Thomä

    The Fanconi anemia (FA) core complex is the ~0.9-mDa ubiquitin ligase most frequently mutated in patients with FA. New cryo-electron microscopy (cryo-EM) data from Shakeel et al. reveals a surprisingly complex ubiquitin ligase architecture, providing unprecedented insight into this critical hub at the interface of DNA crosslink detection and repair.

    更新日期:2020-01-24
  • Stable Isotopes for Tracing Mammalian-Cell Metabolism In Vivo.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-17
    Juan Fernández-García,Patricia Altea-Manzano,Erica Pranzini,Sarah-Maria Fendt

    Metabolism is at the cornerstone of all cellular functions and mounting evidence of its deregulation in different diseases emphasizes the importance of a comprehensive understanding of metabolic regulation at the whole-organism level. Stable-isotope measurements are a powerful tool for probing cellular metabolism and, as a result, are increasingly used to study metabolism in in vivo settings. The additional

    更新日期:2020-01-17
  • In-Cell Discovery of RNA-Protein Interactions.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2020-01-14
    Xavier Sabaté-Cadenas,Alena Shkumatava

    更新日期:2020-01-14
  • Histone Lactylation: A New Role for Glucose Metabolism.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-31
    Maria V Liberti,Jason W Locasale

    Lactate is an end product of glucose metabolism, which serves metabolic and nonmetabolic functions. A new study by Zhang et al. establishes a novel function for lactate whereby it is utilized in a new histone modification, histone lysine lactylation, to regulate gene expression in macrophages.

    更新日期:2019-12-31
  • Reshaping Chromatin Architecture around DNA Breaks.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-24
    Pierre Caron,Sophie E Polo

    DNA double-strand breaks (DSBs) elicit major chromatin changes. Using super-resolution microscopy in human cells, Ochs et al. unveil that the DSB response protein 53BP1 and its effector RIF1 organize DSB-flanking chromatin into circular micro-domains. These structures control the spatial distribution of DSB repair factors safeguarding genome integrity.

    更新日期:2019-12-25
  • Strategies for Engineering and Rewiring Kinase Regulation.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-19
    James W McCormick,David Pincus,Orna Resnekov,Kimberly A Reynolds

    Eukaryotic protein kinases (EPKs) catalyze the transfer of a phosphate group onto another protein in response to appropriate regulatory cues. In doing so, they provide a primary means for cellular information transfer. Consequently, EPKs play crucial roles in cell differentiation and cell-cycle progression, and kinase dysregulation is associated with numerous disease phenotypes including cancer. Nonnative

    更新日期:2019-12-20
  • Linker Domains: Why ABC Transporters 'Live in Fragments no Longer'.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-12
    Robert C Ford,Dominic Marshall-Sabey,John Schuetz

    ATP-binding cassette (ABC) transporters are membrane proteins present in all kingdoms of life. We have considered the disordered region that connects the N- and C-terminal halves in many eukaryotic ABC transporters, allowing all four consensus functional domains to be linked. The recent availability of structures of ABC transporters containing linker regions has allowed us to identify the start and

    更新日期:2019-12-13
  • Computational Dissection of Membrane Transport at a Microscopic Level.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-05
    Tao Jiang,Po-Chao Wen,Noah Trebesch,Zhiyu Zhao,Shashank Pant,Karan Kapoor,Mrinal Shekhar,Emad Tajkhorshid

    Membrane transporters are key gatekeeper proteins at cellular membranes that closely control the traffic of materials. Their function relies on structural rearrangements of varying degrees that facilitate substrate translocation across the membrane. Characterizing these functionally important molecular events at a microscopic level is key to our understanding of membrane transport, yet challenging

    更新日期:2019-12-06
  • The Cytoskeleton as Regulator of Cell Signaling Pathways.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-05
    Ossama Moujaber,Ursula Stochaj

    During interphase, filamentous actin, microtubules, and intermediate filaments regulate cell shape, motility, transport, and interactions with the environment. These activities rely on signaling events that control cytoskeleton properties. Recent studies uncovered mechanisms that go far beyond this one-directional flow of information. Thus, the three branches of the cytoskeleton impinge on signaling

    更新日期:2019-12-05
  • Molecular Mobility-Mediated Regulation of E-Cadherin Adhesion.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-12-04
    Kabir H Biswas

    Cells in epithelial tissues utilize homotypic E-cadherin interaction-mediated adhesions to both physically adhere to each other and sense the physical properties of their microenvironment, such as the presence of other cells in close vicinity or an alteration in the mechanical tension of the tissue. These position E-cadherin centrally in organogenesis and other processes, and its function is therefore

    更新日期:2019-12-04
  • The SLC25 Mitochondrial Carrier Family: Structure and Mechanism.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-29
    Jonathan J Ruprecht,Edmund R S Kunji

    Members of the mitochondrial carrier family (SLC25) provide the transport steps for amino acids, carboxylic acids, fatty acids, cofactors, inorganic ions, and nucleotides across the mitochondrial inner membrane and are crucial for many cellular processes. Here, we use new insights into the transport mechanism of the mitochondrial ADP/ATP carrier to examine the structure and function of other mitochondrial

    更新日期:2019-11-30
  • Striking Diversity of Mitochondria-Specific Translation Processes across Eukaryotes.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-25
    Florent Waltz,Philippe Giegé

    Mitochondria are essential organelles that act as energy conversion powerhouses and metabolic hubs. Their gene expression machineries combine traits inherited from prokaryote ancestors and specific features acquired during eukaryote evolution. Mitochondrial research has wide implications ranging from human health to agronomy. We highlight recent advances in mitochondrial translation. Functional, biochemical

    更新日期:2019-11-26
  • The Brain Epigenome Goes Drunk: Alcohol Consumption Alters Histone Acetylation and Transcriptome.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-22
    Irene de Diego,Annika Müller-Eigner,Shahaf Peleg

    Recent studies demonstrated that alcohol consumption can induce epigenetic changes in the brain, although the exact mechanism underlying such changes remained unclear. Now, a report by Mews et al. shows a direct link between alcohol consumption and histone acetylation changes in the brain, which are mediated by the neuronal acetyl-CoA synthase, ACSS2.

    更新日期:2019-11-22
  • New Structures Reveal Interaction Dynamics in Respiratory Supercomplexes.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-19
    Peter Brzezinski

    Mitochondrial energy conversion involves a chain of membrane-bound proteins that are wired to conduct an electron current, which drives transmembrane proton translocation. These enzymes associate to form supercomplexes, but the functional relevance of the higher-order structures is unknown. A recent study by Letts et al. presents structures of a supercomplex, which suggest how the interaction choreography

    更新日期:2019-11-19
  • Expansion and Cell-Cycle Arrest: Common Denominators of Cellular Senescence.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-07-22
    Mikolaj Ogrodnik,Hanna Salmonowicz,Diana Jurk,João F Passos

    Cellular senescence is a major driver of age-related diseases, and senotherapies are being tested in clinical trials. Despite its popularity, cellular senescence is weakly defined and is frequently referred to as irreversible cell-cycle arrest. In this article we hypothesize that cellular senescence is a phenotype that results from the coordination of two processes: cell expansion and cell-cycle arrest

    更新日期:2019-11-18
  • Conservation and Variability of the AUG Initiation Codon Context in Eukaryotes
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-07-25
    Greco Hernández, Vincent G. Osnaya, Xochitl Pérez-Martínez

    Selection of the translation initiation site (TIS) is a crucial step during translation. In the 1980s Marylin Kozak performed key studies on vertebrate mRNAs to characterize the optimal TIS consensus sequence, the Kozak motif. Within this motif, conservation of nucleotides in crucial positions, namely a purine at −3 and a G at +4 (where the A of the AUG is numbered +1), is essential for TIS recognition

    更新日期:2019-11-18
  • Engineering Metalloprotein Functions in Designed and Native Scaffolds
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-07-13
    Flavia Nastri, Daniele D’Alonzo, Linda Leone, Gerardo Zambrano, Vincenzo Pavone, Angela Lombardi

    Metalloproteins are crucial for life. The mutual relationship between metal ions and proteins makes metalloproteins able to accomplish key processes in biological systems, often very difficult to reproduce with inorganic coordination compounds under mild conditions. Taking inspiration from nature, many efforts have been devoted to developing artificial molecules as metalloprotein mimics. We have witnessed

    更新日期:2019-11-18
  • Nutrient Zinc at the Host-Pathogen Interface.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-07-17
    Zachery R Lonergan,Eric P Skaar

    Zinc is an essential cofactor required for life and, as such, mechanisms exist for its homeostatic maintenance in biological systems. Despite the evolutionary distance between vertebrates and microbial life, there are parallel mechanisms to balance the essentiality of zinc with its inherent toxicity. Vertebrates regulate zinc homeostasis through a complex network of metal transporters and buffering

    更新日期:2019-11-18
  • Do All Roads Lead to Rome in G-Protein Activation?
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-18
    Pradipta Ghosh,Mikel Garcia-Marcos

    High-resolution structural studies on G-protein-coupled receptors (GPCRs) have flourished recently, providing long-sought insights into the dynamic process of guanine nucleotide-binding protein (G-protein) activation. In parallel, analogous studies are starting to shed light on how the same G-proteins are activated by non-GPCR proteins. Can we learn about common themes and variations in G-protein activation

    更新日期:2019-11-18
  • Dynamic Interplay between miRNAs and the Extracellular Matrix Influences the Tumor Microenvironment
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-07-06
    Zoi Piperigkou, Nikos K. Karamanos

    Expression of miRNAs is critical for the regulation of several cell functions including proliferation, migration, differentiation, and survival, as well as extracellular matrix (ECM) remodeling. The dynamic interplay between miRNAs, ECM macromolecules, and the tumor microenvironment plays critical roles in many aspects of human diseases such as metabolic disorders and cancers. Circulating and secreted

    更新日期:2019-11-18
  • Functional Diversification of ER Stress Responses in Arabidopsis.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-18
    Noelia Pastor-Cantizano,Dae Kwan Ko,Evan Angelos,Yunting Pu,Federica Brandizzi

    The endoplasmic reticulum (ER) is responsible for the synthesis of one-third of the cellular proteome and is constantly challenged by physiological and environmental situations that can perturb its homeostasis and lead to the accumulation of misfolded secretory proteins, a condition referred to as ER stress. In response, the ER evokes a set of intracellular signaling processes, collectively known as

    更新日期:2019-11-18
  • Switching Condensates: The CTD Code Goes Liquid.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-13
    Bede Portz,James Shorter

    Condensates containing RNA polymerase II (Pol II) materialize at sites of active transcription. Young and coworkers now establish that C-terminal domain phosphorylation regulates Pol II partitioning into distinct condensates connected with transcription initiation or splicing. This advance hints that distinct condensates with specialized functional compositions might choreograph distinct stages of

    更新日期:2019-11-13
  • Netrin Synergizes Signaling and Adhesion through DCC.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-05
    Rob Meijers,Robert G Smock,Yan Zhang,Jia-Huai Wang

    Netrin is a prototypical axon guidance cue. Structural studies have revealed how netrin interacts with the deleted in colorectal cancer (DCC) receptor, other receptors, and co-factors for signaling. Recently, genetic studies suggested that netrin is involved in neuronal haptotaxis, which requires a reversible adhesion process. Structural data indicate that netrin can also mediate trans-adhesion between

    更新日期:2019-11-06
  • Running the Light: Nucleotide Metabolism Drives Bypass of Senescence in Cancer
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-04
    Christopher J. Halbrook, Daniel R. Wahl, Costas A. Lyssiotis

    Senescence is engaged in response to oncogenes to suppress proliferation. Cancers rewire metabolism to facilitate proliferation; however, it is not well appreciated how this enables senescence bypass. Recent work by Buj et al. demonstrates that loss of the tumor suppressor p16 engages a mTORC1-dependent increase in nucleotide pools to override senescence.

    更新日期:2019-11-04
  • Renaissance of Allostery to Disrupt Protein Kinase Interactions.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-02
    Alejandro E Leroux,Ricardo M Biondi

    Protein-protein interactions often regulate the activity of protein kinases by allosterically modulating the conformation of the ATP-binding site. Bidirectional allostery implies that reverse modulation (i.e., from the ATP-binding site to the interaction and regulatory sites) must also be possible. Here, we review both the allosteric regulation of protein kinases and recent work describing how compounds

    更新日期:2019-11-04
  • Bacterial RNA Degradosomes: Molecular Machines under Tight Control.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-01
    Alejandro Tejada-Arranz,Valérie de Crécy-Lagard,Hilde de Reuse

    Bacterial RNA degradosomes are multienzyme molecular machines that act as hubs for post-transcriptional regulation of gene expression. The ribonuclease activities of these complexes require tight regulation, as they are usually essential for cell survival while potentially destructive. Recent studies have unveiled a wide variety of regulatory mechanisms including autoregulation, post-translational

    更新日期:2019-11-01
  • Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-01
    Ram Prasad Bhusal,James R O Eaton,Sayeeda T Chowdhury,Christine A Power,Amanda E I Proudfoot,Martin J Stone,Shoumo Bhattacharya

    Ticks are hematophagous arachnids that parasitize mammals and other hosts, feeding on their blood. Ticks secrete numerous salivary factors that enhance host blood flow or suppress the host inflammatory response. The recruitment of leukocytes, a hallmark of inflammation, is regulated by chemokines, which activate chemokine receptors on the leukocytes. Ticks target this process by secreting glycoproteins

    更新日期:2019-11-01
  • Strategies for Development of a Next-Generation Protein Sequencing Platform.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-10-30
    Nicholas Callahan,Jennifer Tullman,Zvi Kelman,John Marino

    Proteomic analysis can be a critical bottleneck in cellular characterization. The current paradigm relies primarily on mass spectrometry of peptides and affinity reagents (i.e., antibodies), both of which require a priori knowledge of the sample. An unbiased protein sequencing method, with a dynamic range that covers the full range of protein concentrations in proteomes, would revolutionize the field

    更新日期:2019-11-01
  • Deciphering Gene Regulation Using Massively Parallel Reporter Assays.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-11
    Max Trauernicht,Miguel Martinez-Ara,Bas van Steensel

    更新日期:2019-11-01
  • Contact Mapping to Unravel Chromosome Folding.
    Trends Biochem. Sci. (IF 16.889) Pub Date : 2019-11-05
    Tiffany Ge,Celeste D Rosencrance,Kyle P Eagen

    更新日期:2019-11-01
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