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Trends in Cell Biology

Arthur J Lustig
A mechanistic understanding of the yeast telomere requires an integrated understanding of telomere chromatin structure (telosomes), telomeric origins of replications, telomere length homeostasis, and telosome epigenetics. Recent molecular and genetic studies of the yeast telosomal components Rap1, Rif1, and Rif2, the Mre11 complex, and Tel1ATM promise to increase our insight into the coordination between these processes. Here, an intricate relationship is proposed between these multiple components that has resulted in increased appreciation of the multiple levels of telomere length control and their differentiation from double-strand repair...
February 11, 2019: Trends in Cell Biology
Ilio Vitale, Antonella Sistigu, Gwenola Manic, Nils-Petter Rudqvist, Zlatko Trajanoski, Lorenzo Galluzzi
Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies...
February 11, 2019: Trends in Cell Biology
Brice Laffleur, Uttiya Basu
The 'RNA world', in which RNA molecules stored information and acquired enzymatic properties, has been proposed to have preceded organism life. RNA is now recognized for its central role in biology, with accumulating evidence implicating coding and noncoding (nc)RNAs in myriad mechanisms regulating cellular physiology and disequilibrium in transcriptomes resulting in pathological conditions. Nascently synthesized RNAs are subjected to stringent regulation by sophisticated RNA surveillance pathways. In this review, we integrate these pathways from a developmental viewpoint, proposing RNA surveillance as the convergence of mechanisms that ensure the exact titration of RNA molecules in a spatiotemporally controlled manner, leading to development without the onset of pathological conditions, including cancer...
February 9, 2019: Trends in Cell Biology
Federico Gulluni, Maria Chiara De Santis, Jean Piero Margaria, Miriam Martini, Emilio Hirsch
The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate inositol phospholipids, thereby controlling membrane lipid composition and regulating a wide range of intracellular processes, including vesicular trafficking and signal transduction. Despite the vast knowledge on class I PI3Ks, recent studies are only now revealing the importance of class II PI3Ks in cell proliferation, survival, and migration. Increasing evidence suggests that the three class II PI3Ks isoforms (PI3K-C2α, PI3K-C2β, and PI3K-C2γ) have distinct and non-overlapping cellular roles...
January 25, 2019: Trends in Cell Biology
Sebastian Rumpf, Neele Wolterhoff, Svende Herzmann
Large-scale neurite pruning, the developmentally regulated degeneration of axons or dendrites, is an important specificity mechanism during neuronal circuit formation. Pruning is usually restricted to single neurite branches and can occur by local degeneration or retraction. How this spatial regulation is achieved, and what triggers degeneration locally, are still poorly understood. At the cellular level, pruning involves local cytoskeleton disassembly before branch removal. Recent evidence suggests that microtubule disassembly is the local trigger and that the specific local microtubule organization of axons or dendrites determines where and how neurites degenerate...
January 22, 2019: Trends in Cell Biology
Francesco Napoletano, Olga Baron, Peter Vandenabeele, Bertrand Mollereau, Manolis Fanto
In multicellular organisms, cell death is an essential aspect of life. Over the past decade, the spectrum of different forms of regulated cell death (RCD) has expanded dramatically with relevance in several pathologies such as inflammatory and neurodegenerative diseases. This has been paralleled by the growing awareness of the central importance of autophagy as a stress response that influences decisions of cell life and cell death. Here, we first introduce criteria and methodologies for correct identification of the different RCD forms...
January 18, 2019: Trends in Cell Biology
Lin Guo, Charlotte M Fare, James Shorter
Nuclear-import receptors (NIRs) bind nuclear-localization signals (NLSs) of protein cargo in the cytoplasm and transport them into the nucleus. Here, we review advances establishing that NIRs also function in the cytoplasm to prevent and reverse functional and aberrant phase transitions of their cargo, including neurodegenerative disease-linked RNA-binding proteins (RBPs) with prion-like domains, such as TDP-43, FUS, hnRNPA1, and hnRNPA2. NIRs selectively extract cargo from condensed liquid phases thereby regulating functional phase separation...
January 16, 2019: Trends in Cell Biology
María Isabel Vaquero-Sedas, Miguel Ángel Vega-Palas
The integrity of the chromatin associated with telomeric regions, which include telomeres and subtelomeres, is essential for telomeres function and cell viability. Whereas human subtelomeres are heterochromatic, telomeres are labeled with euchromatic marks like H4K20me1 and H3K27ac in most commonly studied human cell lines. The epigenetic marks of human telomeric regions influence oncogenic processes. Indeed, different drugs that decrease their genome-wide levels are currently being used or tested in specific cancer therapies...
January 16, 2019: Trends in Cell Biology
Andrea Becchetti, Giulia Petroni, Annarosa Arcangeli
Cell-matrix adhesion determines the choice between different cell fates and is accompanied by substantial changes in ion transport. The greatest evidence is the bidirectional interplay occurring between integrin receptors and K+ channels. These proteins can form signaling hubs that regulate cell proliferation, differentiation, and migration in normal and neoplastic tissue. Recent results show that the physical interaction with integrins determines the balance of the open and closed K+ channel states, and individual channel conformations regulate distinct downstream pathways...
January 8, 2019: Trends in Cell Biology
Ryu-Suke Nozawa, Nick Gilbert
A significant amount of RNA is present in the nucleus of mammalian cells but only a small proportion of it is destined for the cytoplasm and subsequent translation, leaving much RNA to associate with chromatin. Historically, nuclear RNA was thought to interact with proteins to form a filamentous nuclear matrix, but this idea became less popular as more dynamic models of chromatin behaviour became more prevalent. Using new molecular and imaging approaches it is becoming clear that RNA should be considered an integral component of nuclear organisation; it is transcriptionally responsive and interacts with abundant nuclear RNA-binding proteins...
January 7, 2019: Trends in Cell Biology
Kem A Sochacki, Justin W Taraska
Clathrin-mediated endocytosis (CME) is the primary mechanism eukaryotic cells use to internalize material. New imaging tools are revealing the nanoscale structural dynamics of single clathrin-coated sites. Recently, it has become clear that the structure and dynamics of clathrin - flat clathrin lattices and the transition to highly curved clathrin-coated vesicles - are adaptable and can follow many paths. Thus, understanding this dynamic plasticity will lead to insights into how one molecular machine can participate in multiple pathways and adapt to changing and diverse cellular environments...
December 28, 2018: Trends in Cell Biology
Ievgenia Pastushenko, Cédric Blanpain
Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features. In cancer, EMT is associated with tumor initiation, invasion, metastasis, and resistance to therapy. Recently, it has been demonstrated that EMT is not a binary process, but occurs through distinct cellular states. Here, we review the recent studies that demonstrate the existence of these different EMT states in cancer and the mechanisms regulating their functions. We discuss the different functional characteristics, such as proliferation, propagation, plasticity, invasion, and metastasis associated with the distinct EMT states...
December 26, 2018: Trends in Cell Biology
Dongwei Li, Jiekai Chen, Duanqing Pei
No abstract text is available yet for this article.
December 10, 2018: Trends in Cell Biology
John R Jimah, Jenny E Hinshaw
Dynamin superfamily proteins (DSPs) mediate membrane fission and fusion necessary for endocytosis, organelle biogenesis and maintenance, as well as for bacterial cytokinesis. They also function in the innate immune response to pathogens and in organizing the cytoskeleton. In this review, we summarize the current understanding of the molecular mechanism of DSPs, with emphasis on the structural basis of function. Studies from the past decade on the structure and mechanism of DSPs enable comparative analysis of shared mechanisms and unique features of this protein family...
December 5, 2018: Trends in Cell Biology
Anne Hahn, Steven Zuryn
Mitochondrial genome (mitochondrial DNA, mtDNA) lesions that unbalance bioenergetic and oxidative outputs are an important cause of human disease. A major impediment in our understanding of the pathophysiology of mitochondrial disorders is the complexity with which mtDNA mutations are spatiotemporally distributed and managed within individual cells, tissues, and organs. Unlike the comparatively static nuclear genome, accumulating evidence highlights the variability, dynamism, and modifiability of the mtDNA nucleotide sequence between individual cells over time...
November 30, 2018: Trends in Cell Biology
Angela L Nicholson, Amy E Pasquinelli
Poly(A) tails are non-templated additions of adenosines at the 3' ends of most eukaryotic mRNAs. In the nucleus, these RNAs are co-transcriptionally cleaved at a poly(A) site and then polyadenylated before being exported to the cytoplasm. In the cytoplasm, poly(A) tails play pivotal roles in the translation and stability of the mRNA. One challenge in studying poly(A) tails is that they are difficult to sequence and accurately measure. However, recent advances in sequencing technology, computational algorithms, and other assays have enabled a more detailed look at poly(A) tail length genome-wide throughout many developmental stages and organisms...
November 29, 2018: Trends in Cell Biology
Tania Morán Luengo, Matthias P Mayer, Stefan G D Rüdiger
Conserved families of molecular chaperones assist protein folding in the cell. Here we review the conceptual advances on three major folding routes: (i) spontaneous, chaperone-independent folding; (ii) folding assisted by repetitive Hsp70 cycles; and (iii) folding by the Hsp70-Hsp90 cascades. These chaperones prepare their protein clients for folding on their own, without altering their folding path. A particularly interesting role is reserved for Hsp90. The function of Hsp90 in folding is its ancient function downstream of Hsp70, free of cochaperone regulation and present in all kingdoms of life...
November 28, 2018: Trends in Cell Biology
Aurèle Piazza, Wolf-Dietrich Heyer
The maintenance of genome integrity involves multiple independent DNA damage avoidance and repair mechanisms. However, the origin and pathways of the focal chromosomal reshuffling phenomena collectively referred to as chromothripsis remain mechanistically obscure. We discuss here the role, mechanisms, and regulation of homologous recombination (HR) in the formation of simple and complex chromosomal rearrangements. We emphasize features of the recently characterized multi-invasion (MI)-induced rearrangement (MIR) pathway which uniquely amplifies the initial DNA damage...
November 26, 2018: Trends in Cell Biology
Robin Ferrari, Elvira Infante, Philippe Chavrier
Matrix proteolysis mediated by MT1-MMP facilitates the invasive migration of tumor cells in dense tissues, which otherwise get trapped in the matrix because of limited nuclear deformability. A digest-on-demand response has been identified, which requires nucleus-microtubule linkage through the LINC complex and triggers MT1-MMP surface-exposure to facilitate nucleus movement.
February 2019: Trends in Cell Biology
Edmond R Watson, Nicholas G Brown, Jan-Michael Peters, Holger Stark, Brenda A Schulman
The anaphase promoting complex/cyclosome (APC/C) E3 ligase controls mitosis and nonmitotic pathways through interactions with proteins that coordinate ubiquitylation. Since the discovery that the catalytic subunits of APC/C are conformationally dynamic cullin and RING proteins, many unexpected and intricate regulatory mechanisms have emerged. Here, we review structural knowledge of this regulation, focusing on: (i) coactivators, E2 ubiquitin (Ub)-conjugating enzymes, and inhibitors engage or influence multiple sites on APC/C including the cullin-RING catalytic core; and (ii) the outcomes of these interactions rely on mobility of coactivators and cullin-RING domains, which permits distinct conformations specifying different functions...
February 2019: Trends in Cell Biology
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