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You searched for: Journal Molecular cell Remove constraint Journal: Molecular cell Publication Year 2017 Remove constraint Publication Year: 2017 Source 2017 v.68 no.2 Remove constraint Source: 2017 v.68 no.2
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1. A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants

Author:
Gabrielsen, Mads; Buetow, Lori; Nakasone, Mark A.; Ahmed, Syed Feroj; Sibbet, Gary J.; Smith, Brian O.; Zhang, Wei; Sidhu, Sachdev S.; Huang, Danny T.
Source:
Molecular cell 2017 v.68 no.2 pp. 456-470.e10
ISSN:
1097-2765
Subject:
binding sites; ubiquitin; ubiquitin-protein ligase
Abstract:
... RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemi ...
DOI:
10.1016/j.molcel.2017.09.027
PubMed:
29053960
PubMed Central:
PMC5655547

2. Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling

Author:
Tan, Peng; He, Lian; Cui, Jun; Qian, Chen; Cao, Xin; Lin, Meng; Zhu, Qingyuan; Li, Yinyin; Xing, Changsheng; Yu, Xiao; Wang, Helen Y.; Wang, Rong-Fu
Source:
Molecular cell 2017 v.68 no.2 pp. 293-307.e5
ISSN:
1097-2765
Subject:
RNA interference; adenosinetriphosphatase; dephosphorylation; immunity; lysine; mitochondria; signalosome; two hybrid system techniques
Abstract:
... Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor pro ...
DOI:
10.1016/j.molcel.2017.09.035

3. CDK4 Phosphorylates AMPKα2 to Inhibit Its Activity and Repress Fatty Acid Oxidation

Author:
Lopez-Mejia, Isabel C.; Lagarrigue, Sylviane; Giralt, Albert; Martinez-Carreres, Laia; Zanou, Nadège; Denechaud, Pierre-Damien; Castillo-Armengol, Judit; Chavey, Carine; Orpinell, Meritxell; Delacuisine, Brigitte; Nasrallah, Anita; Collodet, Caterina; Zhang, Lianjun; Viollet, Benoît; Hardie, D. Grahame; Fajas, Lluis
Source:
Molecular cell 2017 v.68 no.2 pp. 336-349.e6
ISSN:
1097-2765
Subject:
AMP-activated protein kinase; aerobiosis; beta oxidation; cell cycle; cyclin-dependent kinase; exercise; fibroblasts; glycolysis; mice; mutants; myotubes; protein phosphorylation; skeletal muscle
Abstract:
... The roles of CDK4 in the cell cycle have been extensively studied, but less is known about the mechanisms underlying the metabolic regulation by CDK4. Here, we report that CDK4 promotes anaerobic glycolysis and represses fatty acid oxidation in mouse embryonic fibroblasts (MEFs) by targeting the AMP-activated protein kinase (AMPK). We also show that fatty acid oxidation (FAO) is specifically induc ...
DOI:
10.1016/j.molcel.2017.09.034

4. Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress

Author:
Gan, Haiyun; Yu, Chuanhe; Devbhandari, Sujan; Sharma, Sushma; Han, Junhong; Chabes, Andrei; Remus, Dirk; Zhang, Zhiguo
Source:
Molecular cell 2017 v.68 no.2 pp. 446-455.e3
ISSN:
1097-2765
Subject:
DNA helicases; DNA replication; DNA-directed DNA polymerase; single-stranded DNA
Abstract:
... The checkpoint kinase Rad53 is activated during replication stress to prevent fork collapse, an essential but poorly understood process. Here we show that Rad53 couples leading- and lagging-strand synthesis under replication stress. In rad53-1 cells stressed by dNTP depletion, the replicative DNA helicase, MCM, and the leading-strand DNA polymerase, Pol ε, move beyond the site of DNA synthesis, li ...
DOI:
10.1016/j.molcel.2017.09.018
PubMed:
29033319
PubMed Central:
PMC5802358

5. Histone H3 Dual Ubiquitylation Mediates Maintenance DNA Methylation

Author:
Vann, Kendra R.; Kutateladze, Tatiana G.
Source:
Molecular cell 2017 v.68 no.2 pp. 261-262
ISSN:
1097-2765
Subject:
DNA methylation; epigenetics; histones; post-translational modification
Abstract:
... Epigenetic marks, including DNA methylation and posttranslational modifications (PTMs) in histones, are important factors in determining the fate of replicating cells. In this issue of Molecular Cell, Ishiyama et al. (2017) reveal yet another layer in a remarkably complex mechanism of maintenance DNA methylation. ...
DOI:
10.1016/j.molcel.2017.10.007

6. Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells

Author:
Liu, Kai; Lee, Jiyoung; Kim, Ja Yeon; Wang, Linya; Tian, Yongjun; Chan, Stephanie T.; Cho, Cecilia; Machida, Keigo; Chen, Dexi; Ou, Jing-Hsiung James
Source:
Molecular cell 2017 v.68 no.2 pp. 281-292.e5
ISSN:
1097-2765
Subject:
hepatoma; mitochondria; mitophagy; stem cells; transcription factors
Abstract:
... Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mi ...
DOI:
10.1016/j.molcel.2017.09.022
PubMed:
29033320
PubMed Central:
PMC5687282

7. mTORC1 Phosphorylates Acetyltransferase p300 to Regulate Autophagy and Lipogenesis

Author:
Wan, Wei; You, Zhiyuan; Xu, Yinfeng; Zhou, Li; Guan, Zhunlv; Peng, Chao; Wong, Catherine C.L.; Su, Hua; Zhou, Tianhua; Xia, Hongguang; Liu, Wei
Source:
Molecular cell 2017 v.68 no.2 pp. 323-335.e6
ISSN:
1097-2765
Subject:
acetylation; acetyltransferases; amino acid sequences; autophagy; cell growth; histones; lipogenesis; mammals; phosphorylation; serine
Abstract:
... Acetylation is increasingly recognized as one of the major post-translational mechanisms for the regulation of multiple cellular functions in mammalian cells. Acetyltransferase p300, which acetylates histone and non-histone proteins, has been intensively studied in its role in cell growth and metabolism. However, the mechanism underlying the activation of p300 in cells remains largely unknown. Her ...
DOI:
10.1016/j.molcel.2017.09.020

8. Regulation of m6A Transcripts by the 3ʹ→5ʹ RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline

Author:
Wojtas, Magdalena Natalia; Pandey, Radha Raman; Mendel, Mateusz; Homolka, David; Sachidanandam, Ravi; Pillai, Ramesh S.
Source:
Molecular cell 2017 v.68 no.2 pp. 374-387.e12
ISSN:
1097-2765
Subject:
RNA helicases; RNA splicing; adenosinetriphosphatase; enzyme activity; female fertility; gene expression; germ cells; males; meiosis; messenger RNA; mice; mutants; proteins; testes; transcriptome
Abstract:
... N⁶-methyladenosine (m⁶A) is an essential internal RNA modification that is critical for gene expression control in most organisms. Proteins with a YTH domain recognize m⁶A marks and are mediators of molecular functions like RNA splicing, mRNA decay, and translation control. Here we demonstrate that YTH domain-containing 2 (YTHDC2) is an m⁶A reader that is essential for male and female fertility in ...
DOI:
10.1016/j.molcel.2017.09.021

9. Restoration of Replication Fork Stability in BRCA1- and BRCA2-Deficient Cells by Inactivation of SNF2-Family Fork Remodelers

Author:
Taglialatela, Angelo; Alvarez, Silvia; Leuzzi, Giuseppe; Sannino, Vincenzo; Ranjha, Lepakshi; Huang, Jen-Wei; Madubata, Chioma; Anand, Roopesh; Levy, Brynn; Rabadan, Raul; Cejka, Petr; Costanzo, Vincenzo; Ciccia, Alberto
Source:
Molecular cell 2017 v.68 no.2 pp. 414-430.e8
ISSN:
1097-2765
Subject:
DNA; DNA damage; DNA repair; DNA replication; chromosome aberrations; genome; genomics; tumor suppressor proteins
Abstract:
... To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DN ...
DOI:
10.1016/j.molcel.2017.09.036
PubMed:
29053959
PubMed Central:
PMC5720682

10. Ribosome Collision Is Critical for Quality Control during No-Go Decay

Author:
Simms, Carrie L.; Yan, Liewei L.; Zaher, Hani S.
Source:
Molecular cell 2017 v.68 no.2 pp. 361-373.e5
ISSN:
1097-2765
Subject:
messenger RNA; models; ribosomal proteins; ribosomes; start codon; translation (genetics); ubiquitination
Abstract:
... No-go decay (NGD) is a eukaryotic quality control mechanism that evolved to cope with translational arrests. The process is characterized by an endonucleolytic cleavage near the stall sequence, but the mechanistic details are unclear. Our analysis of cleavage sites indicates that cleavage requires multiple ribosomes on the mRNA. We also show that reporters harboring stall sequences near the initia ...
DOI:
10.1016/j.molcel.2017.08.019
PubMed:
28943311
PubMed Central:
PMC5659757

11. Spt6 Gets in the Way of Polycomb to Promote ESC Pluripotency

Author:
Robert, François
Source:
Molecular cell 2017 v.68 no.2 pp. 263-264
ISSN:
1097-2765
Subject:
embryonic stem cells; genes; histones
Abstract:
... Despite expressing high levels of Polycomb group proteins, embryonic stem cells (ESCs) are refractory to H3K27 trimethylation, notably at super-enhancers regulating key pluripotency genes. In this issue of Molecular Cell, Wang et al. (2017) report that the histone chaperone Spt6 prevents H3K27 trimethylation of key ESC super-enhancers. ...
DOI:
10.1016/j.molcel.2017.10.005

12. 6S RNA Mimics B-Form DNA to Regulate Escherichia coli RNA Polymerase

Author:
Chen, James; Wassarman, Karen M.; Feng, Shili; Leon, Katherine; Feklistov, Andrey; Winkelman, Jared T.; Li, Zongli; Walz, Thomas; Campbell, Elizabeth A.; Darst, Seth A.
Source:
Molecular cell 2017 v.68 no.2 pp. 388-397.e6
ISSN:
1097-2765
Subject:
DNA; DNA-directed RNA polymerase; Escherichia coli; crosslinking; cryo-electron microscopy; gene expression; non-coding RNA; sugars; transcription (genetics)
Abstract:
... Noncoding RNAs (ncRNAs) regulate gene expression in all organisms. Bacterial 6S RNAs globally regulate transcription by binding RNA polymerase (RNAP) holoenzyme and competing with promoter DNA. Escherichia coli (Eco) 6S RNA interacts specifically with the housekeeping σ⁷⁰-holoenzyme (Eσ⁷⁰) and plays a key role in the transcriptional reprogramming upon shifts between exponential and stationary phas ...
DOI:
10.1016/j.molcel.2017.09.006
PubMed:
28988932
PubMed Central:
PMC5683422

13. Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage

Author:
Deshpande, Ishan; Seeber, Andrew; Shimada, Kenji; Keusch, Jeremy J.; Gut, Heinz; Gasser, Susan M.
Source:
Molecular cell 2017 v.68 no.2 pp. 431-445.e5
ISSN:
1097-2765
Subject:
DNA damage; models; mutants; single-stranded DNA; yeasts
Abstract:
... Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited through the single-stranded (ss) DNA-binding replication protein A (RPA) to initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the absence of DNA damage is lethal. Therefore, it is important that damage-specific recruitment precedes kinase activation, which is achieved at least in part by Mec1-Ddc2 homo ...
DOI:
10.1016/j.molcel.2017.09.019

14. Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance

Author:
Ishiyama, Satoshi; Nishiyama, Atsuya; Saeki, Yasushi; Moritsugu, Kei; Morimoto, Daichi; Yamaguchi, Luna; Arai, Naoko; Matsumura, Rumie; Kawakami, Toru; Mishima, Yuichi; Hojo, Hironobu; Shimamura, Shintaro; Ishikawa, Fuyuki; Tajima, Shoji; Tanaka, Keiji; Ariyoshi, Mariko; Shirakawa, Masahiro; Ikeguchi, Mitsunori; Kidera, Akinori; Suetake, Isao; Arita, Kyohei; Nakanishi, Makoto
Source:
Molecular cell 2017 v.68 no.2 pp. 350-360.e7
ISSN:
1097-2765
Subject:
DNA methylation; active sites; catalytic activity; crystal structure; histones; hydrophilic interactions; hydrophobicity; ubiquitin
Abstract:
... The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differenc ...
DOI:
10.1016/j.molcel.2017.09.037

15. Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells

Author:
Jin, Shouheng; Tian, Shuo; Luo, Man; Xie, Weihong; Liu, Tao; Duan, Tianhao; Wu, Yaoxing; Cui, Jun
Source:
Molecular cell 2017 v.68 no.2 pp. 308-322.e4
ISSN:
1097-2765
Subject:
autophagy; humans; interferons; lysine; ubiquitin; ubiquitin-protein ligase; viruses
Abstract:
... Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IF ...
DOI:
10.1016/j.molcel.2017.09.005

16. The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins

Author:
Wang, A. Hongjun; Juan, Aster H.; Ko, Kyung Dae; Tsai, Pei-Fang; Zare, Hossein; Dell’Orso, Stefania; Sartorelli, Vittorio
Source:
Molecular cell 2017 v.68 no.2 pp. 398-413.e6
ISSN:
1097-2765
Subject:
acetylation; embryonic stem cells; genomics; histones; messenger RNA; methylation; methyltransferases; nucleosomes; transcription (genetics)
Abstract:
... Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells (ESCs) reduced expression of pluripotency factors, increased expression of cell-lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective downregulation o ...
DOI:
10.1016/j.molcel.2017.09.016
PubMed:
29033324
PubMed Central:
PMC5659763

17. The Met1-Linked Ubiquitin Machinery: Emerging Themes of (De)regulation

Author:
Hrdinka, Matous; Gyrd-Hansen, Mads
Source:
Molecular cell 2017 v.68 no.2 pp. 265-280
ISSN:
1097-2765
Subject:
cell death; immunity; inflammation; mammals; methionine; mutation; neoplasms; transcription factor NF-kappa B; ubiquitin; ubiquitin-protein ligase
Abstract:
... The linear ubiquitin chain assembly complex, LUBAC, is the only known mammalian ubiquitin ligase that makes methionine 1 (Met1)-linked polyubiquitin (also referred to as linear ubiquitin). A decade after LUBAC was discovered as a cellular activity of unknown function, there are now many lines of evidence connecting Met1-linked polyubiquitin to NF-κB signaling, cell death, inflammation, immunity, a ...
DOI:
10.1016/j.molcel.2017.09.001

18. Unexpected Alliance of WHIP-TRIM14-PPP6C to Combat Viruses

Author:
Chen, Weiqiang; Choi, Youn Jung; Jung, Jae U.
Source:
Molecular cell 2017 v.68 no.2 pp. 259-261
ISSN:
1097-2765
Subject:
RNA; signalosome; viruses
Abstract:
... In this issue of Molecular Cell, Tan et al. (2017) provide novel perspectives into the regulatory role of WHIP-TRIM14-PPP6C signalosome in enhancing RIG-I-mediated viral RNA sensing pathway. ...
DOI:
10.1016/j.molcel.2017.10.004