Steven Gygi

Jan 23, 2025 | cell.com | Hao Chen |Cole J. Ferguson |Dylan Mitchell |Isabel Risch |Amanda Titus |João Paulo | +12 more

Keywords ubiquitin deubiquitinase USP7 Hao-Fountain syndrome HAFOUS p53 brain development synapse TMT proteomics Ppil4 RNA splicing Research topic(s) CP: Neuroscience CP: Molecular biology Introduction As a fundamental post-translational modification, protein ubiquitination plays critical roles in neuronal development and function, and deregulation of ubiquitination is thought to contribute to the pathogenesis of diverse neurological conditions, including Angelman,1 Gordon-Holmes,2,3 and...

Aug 1, 2024 | cell.com | Steven Gygi

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May 28, 2024 | cell.com | Valentina Rossio |João Paulo |Xinyue Liu |Steven Gygi

Deubiquitylating enzymes (DUBs) remove ubiquitin from proteins thereby regulating their stability or activity. Our understanding of DUB-substrate specificity is limited because DUBs are typically not compared to each other against many physiological substrates. By broadly inhibiting DUBs in Xenopus egg extract, we generated hundreds of ubiquitylated proteins and compared the ability of 30 DUBs to deubiquitylate them using quantitative proteomics.

Feb 23, 2024 | cell.com | Steven Gygi |Tom A. Rapoport

Highlights•Cdc48 ATPase-dependent proteasomal protein degradation reconstituted in vitro•Substrate shuttling between the proteasome and Cdc48 is mediated by Rad23 and Ubx5•Shp1 stimulates protein unfolding by Cdc48, rather than substrate recruitment•Bidirectional substrate shuttling between the molecular machines occurs in yeastSummaryMost eukaryotic proteins are degraded by the 26S proteasome after modification with a polyubiquitin chain.

Jan 16, 2024 | nature.com | Steven Gygi |Thomas E. Wales |John Engen |James Wells

AbstractBCL-2-associated X protein (BAX) is a promising therapeutic target for activating or restraining apoptosis in diseases of pathologic cell survival or cell death, respectively. In response to cellular stress, BAX transforms from a quiescent cytosolic monomer into a toxic oligomer that permeabilizes the mitochondria, releasing key apoptogenic factors. The mitochondrial lipid trans-2-hexadecenal (t-2-hex) sensitizes BAX activation by covalent derivatization of cysteine 126 (C126).