title: BAP1 is phosphorylated at serine 592 in S-phase following DNA damage.
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.
authors.affiliation: Department of Biochemistry, Emory University, Atlanta, GA 30322, USA.
authors.forename: Ziad M
authors.initials: ZM
authors.lastname: Eletr
authors.forename: Luming
authors.initials: L
authors.lastname: Yin
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilkinson
mesh_terms: D004249:DNA Damage / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016196:S Phase / Q000235:genetics / Q000528:radiation effects; D012694:Serine / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D043222:Ubiquitin Thiolesterase
keywords: BAP1; DNA damage; Deubiquitinating enzyme; Phosphorylation; Ubiquitin