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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
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
Autor:
Paul Clarke
Publikováno v:
Mol Cell
Aberrant cell proliferation is a hallmark of cancer including glioblastoma (GBM). Here we report that protein arginine methyltransferase (PRMT) 6 activity is required for the proliferation, stem-like properties, and tumorigenicity of glioblastoma ste
Autor:
Mikihiko Naito, Keiji Tanaka, Fumiaki Ohtake, Yosuke Demizu, Yoshino Akizuki, Akinori Endo, Ai Kaiho-Soma, Katsuhide Igarashi, Takuji Shoda, Yasushi Saeki, Yasuko Kawase
Publikováno v:
Molecular cell. 81(7)
Targeted protein degradation is an emerging therapeutic paradigm. Small-molecule degraders such as proteolysis-targeting chimeras (PROTACs) induce the degradation of neo-substrates by hijacking E3 ubiquitin ligases. Although ubiquitylation of endogen
Autor:
Neal Rosen, Sarat Chandarlapaty, Sunyana Gadal, Jacob A. Boyer, Radha Mukherjee, Andre Levchenko, Kiran Vanaja, Hilla Solomon
Publikováno v:
Mol Cell
Summary The PI3K pathway regulates cell metabolism, proliferation, and migration, and its dysregulation is common in cancer. We now show that both physiologic and oncogenic activation of PI3K signaling increase the expression of its negative regulato
Autor:
Marius Hedtfeld, Andrea Musacchio, Tanja Bange, Stefano Maffini, Arsen Petrovic, Marion E. Pesenti, Priyanka Singh, Anupallavi Srinivasamani, Sara Carmignani
Publikováno v:
Molecular Cell
Summary Reflecting its pleiotropic functions, Polo-like kinase 1 (PLK1) localizes to various sub-cellular structures during mitosis. At kinetochores, PLK1 contributes to microtubule attachments and mitotic checkpoint signaling. Previous studies ident
Autor:
Hsien Tsung Lai, Kai Ge, Hao Zuo, Cheng Tai Yu, Ming-Jer Tsai, Ji-Eun Lee, Chien Fei Lee, Yihong Wan, Shwu Yuan Wu, Cheng Ming Chiang, Sophia Y. Tsai
Publikováno v:
Mol Cell
Bromodomain-containing protein 4 (BRD4) is a cancer therapeutic target in ongoing clinical trials disrupting primarily BRD4-regulated transcription programs. The role of BRD4 in cancer has been attributed mainly to the abundant long isoform (BRD4-L).
Autor:
Sherman M. Weissman, Wanshan Wang, Bilal Cakir, Young-Jin Kang, Prabir Patra, Eriona Hysolli, Ethan M. Clement, Mei Zhong, Yangfei Xiang, Benjamin Patterson, In-Hyun Park, Yoshiaki Tanaka, Gareth J. Sullivan, Yee Sook Cho, Kun-Yong Kim, Sung Min Hwang, Sang-Hun Lee
Publikováno v:
Mol Cell
Rett syndrome (RTT), mainly caused by mutations in the methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disorders without effective therapeutics. Here, we used two-dimensional and three-dimensional human brain cultures
Autor:
Seung Soo Kim, John Blenis, Gina Lee, Brian F. Pickering, Sungyun Cho, Norbert Perrimon, Jin H. Park, Long He, Lavina Mathur, Cholsoon Jang, Samie R. Jaffrey, Hong-Wen Tang, Joshua D. Rabinowitz, Sunhee Jung, Sebastien Monette
Publikováno v:
Mol Cell
Molecular cell, vol 81, iss 10
Molecular cell, vol 81, iss 10
Dysregulated mTORC1 signaling alters a wide range of cellular processes, contributing to metabolic disorders and cancer. Defining the molecular details of downstream effectors is thus critical for uncovering selective therapeutic targets. We report t