MAPKAP Kinase-2 phosphorylation of PABPC1 controls its interaction with 14-3-3 proteins after DNA damage: A combined kinase and protein array approach.

Autor:	Stehn JR; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Floyd SR; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Wilker EW; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Reinhardt HC; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Clarke SM; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Huang Q; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Polakiewicz RD; Cell Signaling Technology, Danvers, MA, United States., Sonenberg N; Rosalind and Morris Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, QC, Canada., Kong YW; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States., Yaffe MB; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.; Divisions of Surgical Oncology, Trauma, and Surgical Critical Care, Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, MA, United States.; Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2023 Apr 06; Vol. 10, pp. 1148933. Date of Electronic Publication: 2023 Apr 06 (Print Publication: 2023).
DOI:	10.3389/fmolb.2023.1148933
Abstrakt:	14-3-3 proteins play critical roles in controlling multiple aspects of the cellular response to stress and DNA damage including regulation of metabolism, cell cycle progression, cell migration, and apoptotic cell death by binding to protein substrates of basophilic protein kinases following their phosphorylation on specific serine/threonine residues. Although over 200 mammalian proteins that bind to 14-3-3 have been identified, largely through proteomic studies, in many cases the relevant protein kinase responsible for conferring 14-3-3-binding to these proteins is not known. To facilitate the identification of kinase-specific 14-3-3 clients, we developed a biochemical approach using high-density protein filter arrays and identified the translational regulatory molecule PABPC1 as a substrate for Chk1 and MAPKAP Kinase-2 (MK2) in vitro , and for MK2 in vivo , whose phosphorylation results in 14-3-3-binding. We identify Ser-470 on PABPC1 within the linker region connecting the RRM domains to the PABC domain as the critical 14-3-3-binding site, and demonstrate that loss of PABPC1 binding to 14-3-3 results in increased cell proliferation and decreased cell death in response to UV-induced DNA damage. Competing Interests: RP was employed by Cell Signaling Technology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Stehn, Floyd, Wilker, Reinhardt, Clarke, Huang, Polakiewicz, Sonenberg, Kong and Yaffe.)
Databáze:	MEDLINE
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