Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton.

Autor:	Mouery RD; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Lukasik K; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Hsu C; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Bonacci T; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Bolhuis DL; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Wang X; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Mills CA; UNC Proteomics Core Facility, Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Toomer ED; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Canterbury OG; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Robertson KC; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Branigan TB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Brown NG; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Herring LE; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Proteomics Core Facility, Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Gupton SL; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Emanuele MJ; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: emanuele@email.unc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Aug 27; Vol. 43 (8), pp. 114510. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1016/j.celrep.2024.114510
Abstrakt:	Ubiquitination is an essential regulator of cell division. The kinase Polo-like kinase 1 (PLK1) promotes protein degradation at G2/M phase through the E3 ubiquitin ligase Skp1-Cul1-F box (SCF) βTrCP . However, the magnitude to which PLK1 shapes the mitotic proteome is uncharacterized. Combining quantitative proteomics with pharmacologic PLK1 inhibition revealed a widespread, PLK1-dependent program of protein breakdown at G2/M. We validated many PLK1-regulated proteins, including substrates of the cell-cycle E3 SCF Cyclin F , demonstrating that PLK1 promotes proteolysis through at least two distinct E3 ligases. We show that the protein-kinase-A-anchoring protein A-kinase anchor protein 2 (AKAP2) is cell-cycle regulated and that its mitotic degradation is dependent on the PLK1/βTrCP signaling axis. Expression of a non-degradable AKAP2 mutant resulted in actin defects and aberrant mitotic spindles, suggesting that AKAP2 degradation coordinates cytoskeletal organization during mitosis. These findings uncover PLK1's far-reaching role in shaping the mitotic proteome post-translationally and have potential implications in malignancies where PLK1 is upregulated. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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