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Publikováno v:
Mol Cell
Loss of the ataxia-telangiectasia mutated (ATM) kinase causes cerebellum-specific neurodegeneration in humans. We previously demonstrated that deficiency in ATM activation via oxidative stress generates insoluble protein aggregates in human cells, re
Autor:
Elphège P. Nora, Rini Shah
Publikováno v:
Mol Cell
The chromatin fiber folds into loops, but the mechanisms controlling loop extrusion are still poorly understood. Using super-resolution microscopy, we visualize that loops in intact nuclei are formed by a scaffold of cohesin complexes from which the
Autor:
Clerico, Eugenia M., Gierasch, Lila M.
Publikováno v:
Mol Cell
In the eukaryotic cytosol, the Hsp70 and the Hsp90 chaperone machines work in tandem with the maturation of a diverse array of client proteins. The transfer of nonnative clients between these systems is essential to the chaperoning process, but how i
Autor:
Linhan Wang, Jiqiang Li, Qingchen Wang, Man-Xi Ge, Jia Ji, Di Liu, Zhiyuan Wang, Yang Cao, Yaoyang Zhang, Zai-Rong Zhang
Publikováno v:
Molecular cell. 82(18)
Membrane protein clients of endoplasmic reticulum (ER)-associated degradation must be retrotranslocated from the ER membrane by the AAA-ATPase p97 for proteasomal degradation. Before direct engagement with p97, client transmembrane domains (TMDs) tha
Publikováno v:
Molecular Cell
Molecular Cell, 2022, 82 (10), pp.1909-1923.e5. ⟨10.1016/j.molcel.2022.03.017⟩
Molecular Cell, 2022, 82 (10), pp.1909-1923.e5. ⟨10.1016/j.molcel.2022.03.017⟩
International audience; The lack of a consensus DNA sequence defining replication origins in mammals has led researchers to consider chromatin as a means to specify these regions. However, to date, there is no mechanistic understanding of how this co
Autor:
Dhanya Sooraj, Claire Sun, Anh Doan, Daniel J. Garama, Marius V. Dannappel, Danxi Zhu, Hui K. Chua, Sylvia Mahara, Wan Amir Wan Hassan, Yeng Kwang Tay, Aleks Guanizo, Daniel Croagh, Zdenka Prodanovic, Daniel J. Gough, Chunhua Wan, Ron Firestein
Publikováno v:
Molecular cell. 82(1)
Mediator kinases (CDK8/19) are transcriptional regulators broadly implicated in cancer. Despite their central role in fine-tuning gene-expression programs, we find complete loss of CDK8/19 is tolerated in colorectal cancer (CRC) cells. Using orthogon
Autor:
Rebecca Caeser, Triparna Sen
Publikováno v:
Mol Cell
While effective anti-cancer drugs targeting the CHK1 kinase are advancing in the clinic, drug resistance is rapidly emerging. Here, we demonstrate that CRISPR-mediated knockout of the little-known gene FAM122A confers cellular resistance to CHK1 inhi
Autor:
Fatemeh Alikarami, Robert B. Faryabi, Jun Qi, Eugene Khandros, Bin Lu, Alexandra Lenard, Hua Huang, Kathrin M. Bernt, Yeqiao Zhou, Krista A. Budinich, Molly C. Kingsley, Will Bailis, Aoi Wakabayashi, Qingzhou Chen, Junwei Shi, Martin Carroll, Zhendong Cao, Zhen Zhang, Gerd A. Blobel, Diqiu Ren, Shelley L. Berger, Yu-Han Huang
Publikováno v:
Molecular cell. 81(17)
Summary The transformed state in acute leukemia requires gene regulatory programs involving transcription factors and chromatin modulators. Here, we uncover an IRF8-MEF2D transcriptional circuit as an acute myeloid leukemia (AML)-biased dependency. W
Publikováno v:
Mol Cell
The initiation of DNA replication involves cell cycle-dependent assembly and disassembly of protein complexes, including the origin recognition complex (ORC) and CDC6 AAA+ ATPases. We report that multiple short linear protein motifs (SLiMs) within in
Publikováno v:
Molecular cell. 81(11)
The activation of cap-dependent translation in eukaryotes requires multisite, hierarchical phosphorylation of 4E-BP by the 1 MDa kinase mammalian target of rapamycin complex 1 (mTORC1). To resolve the mechanism of this hierarchical phosphorylation at