Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1.

Autor:	Bass TE; Department of Biochemistry, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN., Cortez D; Department of Biochemistry, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN david.cortez@vanderbilt.edu.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2019 Apr 01; Vol. 218 (4), pp. 1235-1249. Date of Electronic Publication: 2019 Feb 12.
DOI:	10.1083/jcb.201810058
Abstrakt:	The ATR kinase controls cell cycle transitions and the DNA damage response. ATR activity is regulated through two ATR-activating proteins, ETAA1 and TOPBP1. To examine how each activator contributes to ATR signaling, we used quantitative mass spectrometry to identify changes in protein phosphorylation in ETAA1- or TOPBP1-deficient cells. We identified 724, 285, and 118 phosphosites to be regulated by TOPBP1, ETAA1, or both ATR activators, respectively. Gene ontology analysis of TOPBP1- and ETAA1-dependent phosphoproteins revealed TOPBP1 to be a primary ATR activator for replication stress, while ETAA1 regulates mitotic ATR signaling. Inactivation of ATR or ETAA1, but not TOPBP1, results in decreased Aurora B kinase activity during mitosis. Additionally, ATR activation by ETAA1 is required for proper chromosome alignment during metaphase and for a fully functional spindle assembly checkpoint response. Thus, we conclude that ETAA1 and TOPBP1 regulate distinct aspects of ATR signaling with ETAA1 having a dominant function in mitotic cells. (© 2019 Bass and Cortez.)
Databáze:	MEDLINE
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