STING channels its proton power
Induction of type I interferon by the STING pathway is a cornerstone of innate immunity. STING also turns on non-canonical autophagy and inflammasome activation although the underlying mechanisms remain ill defined. Liu et al.1 discovered that STING forms a channel that directs proton efflux from the Golgi to drive these responses. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Mingqi Dong, Katherine A. Fitzgerald Tags: Spotlight Source Type: research
How the circadian nuclear orphan receptor REV-ERB α represses transcription: Temporal and spatial phase separation combined
In this issue of Molecular Cell, Zhu et al.1 demonstrate that REV-ERBα and its co-repressor NCOR1 are assembled into daytime-dependent liquid droplets that constitute hubs in which the transcription of multiple REV-ERBα target genes is simultaneously repressed. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Ueli Schibler Tags: Preview Source Type: research
Pulling rank with RNA: RANKL promotes the association of PGC-1 β/RNA complexes with NCoR/HDAC3 to activate gene expression in osteoclasts
In this issue, Abe et al1 report a novel mechanism by which RANKL stimulates osteoclast differentiation and bone resorption through non-coding RNAs that bind PGC-1β and convert the NCoR/HDAC3 co-repressor complex into a co-activator of AP-1- and NFκB-regulated genes. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Haydee M. Torres, Dongwook Yeo, Jennifer J. Westendorf Tags: Preview Source Type: research
Meet the authors: Lizhen Chen, Shasha Chong, and Zhijie “Jason” Liu
Here, Molecular Cell talks to first and co-corresponding author Lizhen Chen and co-corresponding authors Shasha Chong and Zhijie “Jason” Liu about their paper, ‘‘Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions’’ (in this issue of Molecular Cell) and their scientific journeys until now. (Source: Molecular Cell)
Source: Molecular Cell - October 5, 2023 Category: Cytology Authors: Lizhen Chen, Shasha Chong, Zhijie “Jason” Liu Tags: Q & A Source Type: research
ADAR1p150 prevents MDA5 and PKR activation via distinct mechanisms to avert fatal autoinflammation
The A-to-I RNA-editing enzyme ADAR1 has both RNA editing-dependent and -independent functions. Hu et al. report that ADAR1 prevents endogenous dsRNAs from activating both MDA5 and PKR, two innate immune sensors, through distinct mechanisms: editing dsRNAs to prevent MDA5 activation and the competitive binding of dsRNAs to inhibit PKR activation. (Source: Molecular Cell)
Source: Molecular Cell - October 4, 2023 Category: Cytology Authors: Shi-Bin Hu, Jacki Heraud-Farlow, Tao Sun, Zhen Liang, Ankita Goradia, Scott Taylor, Carl R. Walkley, Jin Billy Li Tags: Article Source Type: research
Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair
Wang and Li et al. unveil the intricate regulatory mechanisms of BRCA1-BARD1 ubiquitylation, identify a truly ligase-null variant and another variant specifically impaired in targeting nucleosomal histones, and elucidate the pivotal roles of BRCA1-BARD1 ligase in not only early DNA end resection but also subsequ ent stages in homology-directed repair. (Source: Molecular Cell)
Source: Molecular Cell - October 4, 2023 Category: Cytology Authors: Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O ’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, A Tags: Article Source Type: research
ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei
Joo et al. uncover a surprising role for ATR in promoting rupture of micronuclei (MN). ATR phosphorylates Lamin A/C at S395 and primes S392 for CDK1 phosphorylation, destabilizing the MN envelope. ATR-driven MN rupture activates cGAS and downstream cell-autonomous and cell-non-autonomous processes, prote cting genomic integrity in cell populations. (Source: Molecular Cell)
Source: Molecular Cell - October 2, 2023 Category: Cytology Authors: Yoon Ki Joo, Elizabeth M. Black, Isabelle Trier, Wisse Haakma, Lee Zou, Lilian Kabeche Tags: Article Source Type: research
Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells
He et al. report that MFSD12 upregulation in breast cancer increases the lysosomal cyst(e)ine storage, providing a ready source of cyst(e)ine for GSH synthesis, which is regulated by mTORC1 to fine-tune redox homeostasis and enhance cell fitness. (Source: Molecular Cell)
Source: Molecular Cell - September 25, 2023 Category: Cytology Authors: Lixin He, Jinxin Chen, Pinwei Deng, Shumei Huang, Pian Liu, Chanjuan Wang, Xinjian Huang, Yue Li, Boyu Chen, Dongni Shi, Yunyun Xiao, Xiangfu Chen, Ying Ouyang, Libing Song, Chuyong Lin Tags: Article Source Type: research
Early fate decision for mitochondrially encoded proteins by a molecular triage
Dedicated protein quality control systems ensure the folding of newly synthesized proteins at ribosomes. Kohler et al. reveal such a system for mitochondrially encoded proteins in the form of the PHB/m-AAA protease associated with mitoribosomes. Thereby, interactions with OXPHOS assembly factors or the PHB/m-AAA protease determine the fate of nascent proteins. (Source: Molecular Cell)
Source: Molecular Cell - September 25, 2023 Category: Cytology Authors: Andreas Kohler, Andreas Carlstr öm, Hendrik Nolte, Verena Kohler, Sung-jun Jung, Sagar Sridhara, Takashi Tatsuta, Jens Berndtsson, Thomas Langer, Martin Ott Tags: Article Source Type: research
RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1 β- and RNA-dependent co-activator of osteoclast gene expression
Nuclear receptor co-repressor (NCoR) is found to maintain normal bone density by co-activating RANKL-dependent gene transcription in osteoclasts. Abe et al. resolve this paradox by demonstrating that RANKL induces RNA-dependent assembly of an NCoR/HDAC3/PGC1β complex that co-activates NF-κB and AP-1 target genes required for osteoclast differentiation. (Source: Molecular Cell)
Source: Molecular Cell - September 25, 2023 Category: Cytology Authors: Yohei Abe, Eric R. Kofman, Maria Almeida, Zhengyu Ouyang, Filipa Ponte, Jasmine R. Mueller, Grisel Cruz-Becerra, Mashito Sakai, Thomas A. Prohaska, Nathanael J. Spann, Ana Resende-Coelho, Jason S. Seidman, Joshua D. Stender, Havilah Taylor, Weiwei Fan, Ve Tags: Article Source Type: research
Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions
It is now recognized that multivalent interactions of transcriptional proteins can mediate protein recruitment on enhancers. However, the precise regulation of these interactions remains unclear. By studying androgen-responsive enhancers, Chen et al. show that an optimal level of multivalent interactions of androgen receptor is required for enhancer assembly and activation. (Source: Molecular Cell)
Source: Molecular Cell - September 21, 2023 Category: Cytology Authors: Lizhen Chen, Zhao Zhang, Qinyu Han, Barun K. Maity, Leticia Rodrigues, Emily Zboril, Rashmi Adhikari, Su-Hyuk Ko, Xin Li, Shawn R. Yoshida, Pengya Xue, Emilie Smith, Kexin Xu, Qianben Wang, Tim Hui-Ming Huang, Shasha Chong, Zhijie Liu Tags: Article Source Type: research
Elucidation of E3 ubiquitin ligase specificity through proteome-wide internal degron mapping
Zhang et al. combined a proteome-wide screen with machine learning to identify thousands of short linear motifs (degrons) in human proteins that are associated with sequence-dependent protein degradation. They went on to map critical residues, identify interacting ligases, and validate binding for a divers e collection of internal degrons. (Source: Molecular Cell)
Source: Molecular Cell - September 21, 2023 Category: Cytology Authors: Zhiqian Zhang, Brandon Sie, Aiquan Chang, Yumei Leng, Christopher Nardone, Richard T. Timms, Stephen J. Elledge Tags: Resource Source Type: research
Regulation of nucleo-cytosolic 26S proteasome translocation by aromatic amino acids via mTOR is essential for cell survival under stress
Livneh et al. show that cellular stress, such as amino acid starvation, leads to translocation of the proteasome from the nucleus to the cytosol, where it stimulates proteolysis. The migration is inhibited by Tyr, Trp, and Phe—newly identified mTOR agonists acting via Sestrin3—leading to cell death. (Source: Molecular Cell)
Source: Molecular Cell - September 21, 2023 Category: Cytology Authors: Ido Livneh, Victoria Cohen-Kaplan, Bertrand Fabre, Ifat Abramovitch, Chen Lulu, Nishanth Belugali Nataraj, Ikrame Lazar, Tamar Ziv, Yosef Yarden, Yaniv Zohar, Eyal Gottlieb, Aaron Ciechanover Tags: Article Source Type: research
Implications of a multiscale structure of the yeast nuclear pore complex
Akey et al. report a multiscale structure of the isolated yeast NPC that provides a framework to piece together the roles of nucleoporins in assembly and transport while providing insights into the evolution of critical sub-assemblies. (Source: Molecular Cell)
Source: Molecular Cell - September 21, 2023 Category: Cytology Authors: Christopher W. Akey, Ignacia Echeverria, Christna Ouch, Ilona Nudelman, Yi Shi, Junjie Wang, Brian T. Chait, Andrej Sali, Javier Fernandez-Martinez, Michael P. Rout Tags: Article Source Type: research
Alu transposable elements rewire enhancer-promoter network through RNA pairing
A recent study by Liang et al.1 reveals that interacting enhancer RNAs (eRNAs) and promoter-transcribed upstream antisense RNAs (uaRNAs) can identify enhancer-promoter interactions. Complementary sequences within the interacting eRNAs and uaRNAs, predominantly Alu sequences, confer the specificity for eRNA-uaRNA pairing and hence enhancer-promoter recognition. (Source: Molecular Cell)
Source: Molecular Cell - September 21, 2023 Category: Cytology Authors: Xingzhao Wen, Sheng Zhong Tags: Spotlight Source Type: research
