BAP1 is phosphorylated at serine 592 in S-phase following DNA damage

• Type of Material: Article
• Authors: Ziad M. Eletr, Emory University; Luming Yin, Emory University; Keith Wilkinson, Emory University
• Language: English
• Date: 2013-12-11
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: ©2013 Federation of European Biochemical Societies
• Final Published Version (URL): http://dx.doi.org/10.1016/j.febslet.2013.10.035
• Title of Journal or Parent Work: FEBS Letters
• ISSN: 0014-5793
• Volume: 587
• Issue: 24
• Start Page: 3906
• End Page: 3911
• Grant/Funding Information: This work was supported by the American Cancer Society [grant number 121603-PF-11-144-01-DMC to Z.M.E] and the National Institutes of Health [grant number GM030308 to K.D.W.].
• Keywords: REGULATOR; ASSOCIATION; Phosphorylation; BAP1; CELL-CYCLE; Ubiquitin; BIOPHYSICS; COMPLEX; Science & Technology; UBIQUITIN HYDROLASE; DNA damage; Biophysics; MUTATIONS; Deubiquitinating enzyme; CELL BIOLOGY; TUMOR-SUPPRESSOR; BRCA1-ASSOCIATED PROTEIN-1; MYELOID TRANSFORMATION; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; ATM; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology
• Research Categories: Chemistry, Biochemistry

Abstract

The human BAP1 deubiquitinating enzyme is a chromatin-bound transcriptional regulator and tumor suppressor. BAP1 functions in suppressing cell proliferation, yet its role in the DNA damage response pathway is less understood. In this study we characterized DNA damage-induced phosphorylation of BAP1 at serine 592 (pS592) and the cellular outcomes of this modification. In contrast to the majority of BAP1, pS592-BAP1 is predominantly dissociated from chromatin. Our findings support a model whereby stress induced phosphorylation functions to displace BAP1 from specific promoters. We hypothesize that this regulates the transcription of a subset of genes involved in the response to DNA damage. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.