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http://dx.doi.org/10.1016/j.celrep.2022.111016 | DOI Listing |
J Biol Chem
September 2024
Department of Chemistry, Marquette University, Milwaukee, Wisconsin, USA. Electronic address:
Elife
July 2024
Departments of Biological Sciences and of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, United States.
PIP-dependent Rac exchanger 1 (P-Rex1) is abundantly expressed in neutrophils and plays central roles in chemotaxis and cancer metastasis by serving as a guanine-nucleotide exchange factor (GEF) for Rac. The enzyme is synergistically activated by PIP and heterotrimeric Gβγ subunits, but mechanistic details remain poorly understood. While investigating the regulation of P-Rex1 by PIP, we discovered that Ins(1,3,4,5)P (IP) inhibits P-Rex1 activity and induces large decreases in backbone dynamics in diverse regions of the protein.
View Article and Find Full Text PDFBiochem Soc Trans
August 2024
Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton 3800, Victoria, Australia.
Rho GTPases are a family of highly conserved G proteins that regulate numerous cellular processes, including cytoskeleton organisation, migration, and proliferation. The 20 canonical Rho GTPases are regulated by ∼85 guanine nucleotide exchange factors (GEFs), with the largest family being the 71 Diffuse B-cell Lymphoma (Dbl) GEFs. Dbl GEFs promote GTPase activity through the highly conserved Dbl homology domain.
View Article and Find Full Text PDFNat Cell Biol
September 2024
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Gasdermin (GSDM) family proteins, known as the executors of pyroptosis, undergo protease-mediated cleavage before inducing pyroptosis. We here discovered a form of pyroptosis mediated by full-length (FL) GSDME without proteolytic cleavage. Intense ultraviolet-C irradiation-triggered DNA damage activates nuclear PARP1, leading to extensive formation of poly(ADP-ribose) (PAR) polymers.
View Article and Find Full Text PDFCell Rep
June 2024
Cell Cycle Control Group, University College London (UCL) Cancer Institute, London WC1E 6DD, UK. Electronic address:
The anaphase-promoting complex/cyclosome (APC/C) is a critical and tightly regulated E3 ligase that orchestrates the cellular life cycle by controlling the degradation of cell cycle regulators. An intriguing feature of this complex is an autoinhibition mechanism: an intrinsically disordered loop domain, Apc1-300L, blocks Cdc20 coactivator binding, yet phosphorylation of Apc1-300L counteracts this autoinhibition. Many such disordered loops within APC/C remain unexplored.
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