DUSP7 regulates the activity of ERK2 to promote proper chromosome alignment during cell division.

Autor:	Guo X; Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA., Ramirez I; Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA., Garcia YA; Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA., Velasquez EF; Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA., Gholkar AA; Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA., Cohn W; Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA., Whitelegge JP; Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA; Molecular Biology Institute, University of California, Los Angeles, California, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA., Tofig B; California NanoSystems Institute, University of California, Los Angeles, California, USA., Damoiseaux R; California NanoSystems Institute, University of California, Los Angeles, California, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA., Torres JZ; Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA; Molecular Biology Institute, University of California, Los Angeles, California, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA. Electronic address: torres@chem.ucla.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100676. Date of Electronic Publication: 2021 Apr 16.
DOI:	10.1016/j.jbc.2021.100676
Abstrakt:	Human cell division is a highly regulated process that relies on the accurate capture and movement of chromosomes to the metaphase plate. Errors in the fidelity of chromosome congression and alignment can lead to improper chromosome segregation, which is correlated with aneuploidy and tumorigenesis. These processes are known to be regulated by extracellular signal-regulated kinase 2 (ERK2) in other species, but the role of ERK2 in mitosis in mammals remains unclear. Here, we have identified the dual-specificity phosphatase 7 (DUSP7), known to display selectivity for ERK2, as important in regulating chromosome alignment. During mitosis, DUSP7 bound to ERK2 and regulated the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of DUSP7, but not catalytically inactive mutants, led to a decrease in the levels of phospho-ERK2 and mitotic chromosome misalignment, while knockdown of DUSP7 also led to defective chromosome congression that resulted in a prolonged mitosis. Consistently, knockdown or chemical inhibition of ERK2 or chemical inhibition of the MEK kinase that phosphorylates ERK2 led to chromosome alignment defects. Our results support a model wherein MEK-mediated phosphorylation and DUSP7-mediated dephosphorylation regulate the levels of active phospho-ERK2 to promote proper cell division. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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