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- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.027
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.035
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.034
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.018
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.10.007
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.022
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.020
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.021
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.036
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.08.019
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.10.005
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.006
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.019
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.037
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.005
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.016
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.09.001
- 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
-
https://dx.doi.org/10.1016/j.molcel.2017.10.004