title: USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1.
abstract: Ubiquitin-specific protease 22 (USP22) edits the histone code by deubiquitinating H2A and H2B as part of the mammalian SAGA (Spt-Ada-Gcn5) complex, and is required for transcriptional regulation and normal cell-cycle progression. Here, we show that USP22 affects the expression of p21 by altering far upstream element (FUSE)-binding protein 1 (FBP1) ubiquitination, as ablation of USP22 leads to increased FBP1 ubiquitination and decreased FBP1 protein occupancy at the p21 gene. Surprisingly, increased polyubiquitination of FBP1 does not alter its protein stability, but instead modulates the stable recruitment of FBP1 to target loci. Our results indicate a mechanism by which USP22 regulates cell proliferation and tumorigenesis.
authors.affiliation: Department of Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, 78957, USA.
authors.forename: Boyko S
authors.initials: BS
authors.lastname: Atanassov
authors.forename: Sharon Y R
authors.initials: SY
authors.lastname: Dent
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D006657:Histones; D016601:RNA-Binding Proteins; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human; D004265:DNA Helicases