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You searched for: Journal Molecular cell Remove constraint Journal: Molecular cell Publication Year 2019 Remove constraint Publication Year: 2019 Source 2019 v.74 no.4 Remove constraint Source: 2019 v.74 no.4
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1. A Role for Chromatin Remodeling in Cohesin Loading onto Chromosomes

Author:
Muñoz, Sofía; Minamino, Masashi; Casas-Delucchi, Corella S.; Patel, Harshil; Uhlmann, Frank
Source:
Molecular cell 2019 v.74 no.4 pp. 664-673.e5
ISSN:
1097-2765
Subject:
DNA; DNA repair; DNA-binding proteins; chromatids; chromatin; cohesion; genome; transcription (genetics); yeasts
Abstract:
... Cohesin is a conserved, ring-shaped protein complex that topologically embraces DNA. Its central role in genome organization includes functions in sister chromatid cohesion, DNA repair, and transcriptional regulation. Cohesin loading onto chromosomes requires the Scc2-Scc4 cohesin loader, whose presence on chromatin in budding yeast depends on the RSC chromatin remodeling complex. Here we reveal a ...
DOI:
10.1016/j.molcel.2019.02.027

2. A- Tail of Telomerase RNA Maturation

Author:
Corbett, Anita H.; Fasken, Milo B.
Source:
Molecular cell 2019 v.74 no.4 pp. 635-636
ISSN:
1097-2765
Subject:
RNA; humans; telomerase
Abstract:
... In this issue of Molecular Cell, Roake et al. (2019) define a feedforward kinetic pathway consisting of a cycle of oligoadenylation and deadenylation that regulates the production of mature human telomerase RNA. ...
DOI:
10.1016/j.molcel.2019.04.031

3. Coordinated Conformational Processing of the Tumor Suppressor Protein p53 by the Hsp70 and Hsp90 Chaperone Machineries

Author:
Dahiya, Vinay; Agam, Ganesh; Lawatscheck, Jannis; Rutz, Daniel Andreas; Lamb, Don C.; Buchner, Johannes
Source:
Molecular cell 2019 v.74 no.4 pp. 816-830.e7
ISSN:
1097-2765
Subject:
adenosine triphosphate; genome; hydrolysis; molecular chaperones; tumor suppressor protein p53
Abstract:
... p53, the guardian of the genome, requires chaperoning by Hsp70 and Hsp90. However, how the two chaperone machineries affect p53 conformation and regulate its function remains elusive. We found that Hsp70, together with Hsp40, unfolds p53 in an ATP-dependent reaction. This unfolded state of p53 is susceptible to aggregation after release induced by the nucleotide exchange factor Bag-1. However, whe ...
DOI:
10.1016/j.molcel.2019.03.026

4. C9orf72 Poly(PR) Dipeptide Repeats Disturb Biomolecular Phase Separation and Disrupt Nucleolar Function

Author:
White, Michael R.; Mitrea, Diana M.; Zhang, Peipei; Stanley, Christopher B.; Cassidy, Devon E.; Nourse, Amanda; Phillips, Aaron H.; Tolbert, Michele; Taylor, J. Paul; Kriwacki, Richard W.
Source:
Molecular cell 2019 v.74 no.4 pp. 713-728.e6
ISSN:
1097-2765
Subject:
amyotrophic lateral sclerosis; arginine; cell nucleolus; condensates; dipeptides; droplets; genes; polypeptides; ribosomal RNA; ribosomal proteins; separation; toxicity; translation (genetics)
Abstract:
... Repeat expansion in the C9orf72 gene is the most common cause of the neurodegenerative disorder amyotrophic lateral sclerosis (C9-ALS) and is linked to the unconventional translation of five dipeptide-repeat polypeptides (DPRs). The two enriched in arginine, poly(GR) and poly(PR), infiltrate liquid-like nucleoli, co-localize with the nucleolar protein nucleophosmin (NPM1), and alter the phase sepa ...
DOI:
10.1016/j.molcel.2019.03.019

5. Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein’s C-Terminal Helix

Author:
Topacio, Benjamin R.; Zatulovskiy, Evgeny; Cristea, Sandra; Xie, Shicong; Tambo, Carrie S.; Rubin, Seth M.; Sage, Julien; Kõivomägi, Mardo; Skotheim, Jan M.
Source:
Molecular cell 2019 v.74 no.4 pp. 758-770.e4
ISSN:
1097-2765
Subject:
Animalia; cell division; cell proliferation; cyclin-dependent kinase; cyclins; mutation; neoplasms; phosphorylation
Abstract:
... The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein Rb, which inhibits cell-cycle progression until its inactivation by phosphorylation. However, the role of Rb phosphorylation by cyclin D-Cdk4,6 in cell-cycle progression is unclear because Rb can be phosphorylated by other c ...
DOI:
10.1016/j.molcel.2019.03.020

6. Disruption of Telomerase RNA Maturation Kinetics Precipitates Disease

Author:
Roake, Caitlin M.; Chen, Lu; Chakravarthy, Ananya L.; Ferrell, James E.; Raffa, Grazia D.; Artandi, Steven E.
Source:
Molecular cell 2019 v.74 no.4 pp. 688-700.e3
ISSN:
1097-2765
Subject:
RNA precursors; enzyme activity; fibrosis; germ cells; human diseases; humans; mutation; non-coding RNA; ribonucleases; telomerase
Abstract:
... Mutations in RNA-processing enzymes are increasingly linked to human disease. Telomerase RNA and related noncoding RNAs require 3′ end-processing steps, including oligoadenylation. Germline mutations in poly(A)ribonuclease (PARN) cause accumulation of extended human telomerase RNA (hTR) species and precipitate dyskeratosis congenita and pulmonary fibrosis. Here, we develop nascent RNAend-seq to me ...
DOI:
10.1016/j.molcel.2019.02.033

7. DNA Damage Signaling-Induced Cancer Cell Reprogramming as a Driver of Tumor Relapse

Author:
Filipponi, Doria; Emelyanov, Alexander; Muller, Julius; Molina, Clement; Nichols, Jennifer; Bulavin, Dmitry V.
Source:
Molecular cell 2019 v.74 no.4 pp. 651-663.e8
ISSN:
1097-2765
Subject:
DNA damage; DNA methylation; carcinogenesis; drug therapy; epigenetics; gene expression regulation; humans; loci; mice; neoplasm cells; neoplasms; oncogenes; relapse
Abstract:
... Accumulating evidence supports the role of the DNA damage response (DDR) in the negative regulation of tumorigenesis. Here, we found that DDR signaling poises a series of epigenetic events, resulting in activation of pro-tumorigenic genes but can go as far as reactivation of the pluripotency gene OCT4. Loss of DNA methylation appears to be a key initiating event in DDR-dependent OCT4 locus reactiv ...
DOI:
10.1016/j.molcel.2019.03.002

8. Dual Role of Ribosome-Binding Domain of NAC as a Potent Suppressor of Protein Aggregation and Aging-Related Proteinopathies

Author:
Shen, Koning; Gamerdinger, Martin; Chan, Rebecca; Gense, Karina; Martin, Esther M.; Sachs, Nadine; Knight, Patrick D.; Schlömer, Renate; Calabrese, Antonio N.; Stewart, Katie L.; Leiendecker, Lukas; Baghel, Ankit; Radford, Sheena E.; Frydman, Judith; Deuerling, Elke
Source:
Molecular cell 2019 v.74 no.4 pp. 729-741.e7
ISSN:
1097-2765
Subject:
biogenesis; eukaryotic cells; human diseases; luciferase; models; mutants; protein synthesis
Abstract:
... The nascent polypeptide-associated complex (NAC) is a conserved ribosome-associated protein biogenesis factor. Whether NAC exerts chaperone activity and whether this function is restricted to de novo protein synthesis is unknown. Here, we demonstrate that NAC directly exerts chaperone activity toward structurally diverse model substrates including polyglutamine (PolyQ) proteins, firefly luciferase ...
DOI:
10.1016/j.molcel.2019.03.012

9. Gain of Additional BIRC3 Protein Functions through 3ʹ-UTR-Mediated Protein Complex Formation

Author:
Lee, Shih-Han; Mayr, Christine
Source:
Molecular cell 2019 v.74 no.4 pp. 701-712.e9
ISSN:
1097-2765
Subject:
B-lymphocytes; CXCR4 receptor; RNA-binding proteins; cell movement; leukemia; mass spectrometry; messenger RNA
Abstract:
... Alternative 3ʹ untranslated regions (3ʹ UTRs) are widespread, but their functional roles are largely unknown. We investigated the function of the long BIRC3 3ʹ UTR, which is upregulated in leukemia. The 3ʹ UTR does not regulate BIRC3 protein localization or abundance but is required for CXCR4-mediated B cell migration. We established an experimental pipeline to study the mechanism of regulation an ...
DOI:
10.1016/j.molcel.2019.03.006

10. Gamblers: An Antibiotic-Induced Evolvable Cell Subpopulation Differentiated by Reactive-Oxygen-Induced General Stress Response

Author:
Pribis, John P.; García-Villada, Libertad; Zhai, Yin; Lewin-Epstein, Ohad; Wang, Anthony Z.; Liu, Jingjing; Xia, Jun; Mei, Qian; Fitzgerald, Devon M.; Bos, Julia; Austin, Robert H.; Herman, Christophe; Bates, David; Hadany, Lilach; Hastings, P.J.; Rosenberg, Susan M.
Source:
Molecular cell 2019 v.74 no.4 pp. 785-800.e7
ISSN:
1097-2765
Subject:
DNA; DNA damage; DNA-directed DNA polymerase; Escherichia coli; Food and Drug Administration; antibiotic resistance; antibiotics; cell division; chromosomes; ciprofloxacin; cross resistance; drugs; electron transfer; models; mutagenesis; mutagens; mutants; reactive oxygen species; stress response
Abstract:
... Antibiotics can induce mutations that cause antibiotic resistance. Yet, despite their importance, mechanisms of antibiotic-promoted mutagenesis remain elusive. We report that the fluoroquinolone antibiotic ciprofloxacin (cipro) induces mutations by triggering transient differentiation of a mutant-generating cell subpopulation, using reactive oxygen species (ROS). Cipro-induced DNA breaks activate ...
DOI:
10.1016/j.molcel.2019.02.037

11. Hsp70- and Hsp90-Mediated Regulation of the Conformation of p53 DNA Binding Domain and p53 Cancer Variants

Author:
Boysen, Marta; Kityk, Roman; Mayer, Matthias P.
Source:
Molecular cell 2019 v.74 no.4 pp. 831-843.e4
ISSN:
1097-2765
Subject:
DNA; DNA-binding domains; cell death; conformational isomerization; heat-shock protein 70; heat-shock protein 90; hydrogen; mass spectrometry; molecular conformation; mutants; neoplasms; temperature; ubiquitin-protein ligase
Abstract:
... The activity of the tumor suppressor p53 has to be timed and balanced closely to prevent untimely induction of cell death. The stability of p53 depends on the ubiquitin ligase Mdm2 but also on Hsp70 and Hsp90 chaperones that interact with its DNA binding domain (DBD). Using hydrogen exchange mass spectrometry and biochemical methods, we analyzed conformational states of wild-type p53-DBD at physio ...
DOI:
10.1016/j.molcel.2019.03.032

12. Interleukin-1β Induces mtDNA Release to Activate Innate Immune Signaling via cGAS-STING

Author:
Aarreberg, Lauren D.; Esser-Nobis, Katharina; Driscoll, Connor; Shuvarikov, Andrey; Roby, Justin A.; Gale, Michael
Source:
Molecular cell 2019 v.74 no.4 pp. 801-815.e6
ISSN:
1097-2765
Subject:
cyclic GMP; dengue; epithelial cells; fibroblasts; genes; humans; inflammation; innate immunity; interferon regulatory factor-3; interferons; interleukin-1beta; mitochondrial DNA; nucleotidyltransferases
Abstract:
... Interleukin-1 beta (IL-1β) is a pleiotropic mediator of inflammation and is produced in response to a wide range of stimuli. During infection, IL-1β production occurs in parallel with the onset of innate antimicrobial defenses, but the contribution of IL-1β signaling to cell-intrinsic immunity is not defined. Here, we report that exogenous IL-1β induces interferon regulatory factor 3 (IRF3) activa ...
DOI:
10.1016/j.molcel.2019.02.038

13. MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation

Author:
Baluapuri, Apoorva; Hofstetter, Julia; Dudvarski Stankovic, Nevenka; Endres, Theresa; Bhandare, Pranjali; Vos, Seychelle Monique; Adhikari, Bikash; Schwarz, Jessica Denise; Narain, Ashwin; Vogt, Markus; Wang, Shuang-Yan; Düster, Robert; Jung, Lisa Anna; Vanselow, Jens Thorsten; Wiegering, Armin; Geyer, Matthias; Maric, Hans Michael; Gallant, Peter; Walz, Susanne; Schlosser, Andreas; Cramer, Patrick; Eilers, Martin; Wolf, Elmar
Source:
Molecular cell 2019 v.74 no.4 pp. 674-687.e11
ISSN:
1097-2765
Subject:
DNA-directed RNA polymerase; cell growth; genes; mass spectrometry; mechanism of action; neoplasms; oncogene proteins; peptide elongation factors; transcription (genetics); transcriptional elongation factors
Abstract:
... The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elong ...
DOI:
10.1016/j.molcel.2019.02.031

14. Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation

Author:
Wang, GuoXiao; Meyer, Jesse G.; Cai, Weikang; Softic, Samir; Li, Mengyao Ella; Verdin, Eric; Newgard, Christopher; Schilling, Birgit; Kahn, C. Ronald
Source:
Molecular cell 2019 v.74 no.4 pp. 844-857.e7
ISSN:
1097-2765
Subject:
brown adipose tissue; energy expenditure; glucose; glutamic acid; glutamine; heat production; homeostasis; linear amide hydrolases; mass spectrometry; metabolism; mitochondria; mitophagy; mutation; proteins
Abstract:
... Brown adipose tissue (BAT) is rich in mitochondria and plays important roles in energy expenditure, thermogenesis, and glucose homeostasis. We find that levels of mitochondrial protein succinylation and malonylation are high in BAT and subject to physiological and genetic regulation. BAT-specific deletion of Sirt5, a mitochondrial desuccinylase and demalonylase, results in dramatic increases in gl ...
DOI:
10.1016/j.molcel.2019.03.021

15. The Phospho-Code Determining Circadian Feedback Loop Closure and Output in Neurospora

Author:
Wang, Bin; Kettenbach, Arminja N.; Zhou, Xiaoying; Loros, Jennifer J.; Dunlap, Jay C.
Source:
Molecular cell 2019 v.74 no.4 pp. 771-784.e3
ISSN:
1097-2765
Subject:
Neurospora; cryptochromes; genes; phosphorylation; transactivators
Abstract:
... In the negative feedback loop driving fungal and animal circadian oscillators, negative elements (FREQUENCY [FRQ], PERIODS [PERs], and CRYPTOCHROMES [CRYs]) are understood to inhibit their own expression, in part by promoting the phosphorylation of their heterodimeric transcriptional activators (e.g., White Collar-1 [WC-1]-WC-2 [White Collar complex; WCC] and BMAL1/Circadian Locomotor Output Cycle ...
DOI:
10.1016/j.molcel.2019.03.003

16. ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97

Author:
Wang, Bo; Maxwell, Brian A.; Joo, Joung Hyuck; Gwon, Youngdae; Messing, James; Mishra, Ashutosh; Shaw, Timothy I.; Ward, Amber L.; Quan, Honghu; Sakurada, Sadie Miki; Pruett-Miller, Shondra M.; Bertorini, Tulio; Vogel, Peter; Kim, Hong Joo; Peng, Junmin; Taylor, J. Paul; Kundu, Mondira
Source:
Molecular cell 2019 v.74 no.4 pp. 742-757.e8
ISSN:
1097-2765
Subject:
agonists; autophagy; cytoplasmic granules; mice; muscular diseases; mutation; phosphorylation; therapeutics; ubiquitin; vacuoles
Abstract:
... Disturbances in autophagy and stress granule dynamics have been implicated as potential mechanisms underlying inclusion body myopathy (IBM) and related disorders. Yet the roles of core autophagy proteins in IBM and stress granule dynamics remain poorly characterized. Here, we demonstrate that disrupted expression of the core autophagy proteins ULK1 and ULK2 in mice causes a vacuolar myopathy with ...
DOI:
10.1016/j.molcel.2019.03.027

17. When Degradation Elicits the Alarm: N-Terminal Degradation of NLRP1B Unleashes Its Inflammasome Activity

Author:
Eldeeb, Mohamed A.; Fahlman, Richard P.; Esmaili, Mansoore; Fon, Edward A.
Source:
Molecular cell 2019 v.74 no.4 pp. 637-639
ISSN:
1097-2765
Subject:
immune response; inflammasomes; innate immunity; mammals
Abstract:
... Despite being among the first discovered mammalian innate immune sensor, NLRP1B (NLR pyrin domain-containing1B) activation and its molecular basis have remained elusive. Two recent studies have unveiled N-terminal degradation as a common mechanism for pathogen-mediated NLRP1B inflammasome activation in mammals. ...
DOI:
10.1016/j.molcel.2019.04.032

18. Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers

Author:
Shi, Hailing; Wei, Jiangbo; He, Chuan
Source:
Molecular cell 2019 v.74 no.4 pp. 640-650
ISSN:
1097-2765
Subject:
binding proteins; enzymes; gene expression; mass spectrometry; messenger RNA; metabolism; methylation; nucleosides
Abstract:
... Cellular RNAs are naturally decorated with a variety of chemical modifications. The structural diversity of the modified nucleosides provides regulatory potential to sort groups of RNAs for organized metabolism and functions, thus affecting gene expression. Recent years have witnessed a burst of interest in and understanding of RNA modification biology, thanks to the emerging transcriptome-wide se ...
DOI:
10.1016/j.molcel.2019.04.025