title: PKA/CREB regulates the constitutive promoter activity of the USP22 gene.
abstract: The human ubiquitin-specific processing enzyme 22 (USP22) plays a crucial role in regulating cell cycle processes and its overexpression has been linked to tumor progression. However, the mechanisms leading to USP22 transcriptional activation in human cancer cells are still unclear. Previously, we characterized the 5'-flanking sequence of the human USP22 gene and found a potential CREB/ATF binding site within the basic promoter region. The present study found that this site was required for constitutive USP22 transcriptional activity in HeLa and HepG2 cells. Chromatin immunoprecipitation assay confirmed that CREB interacted with this site. siRNA knockdown of CREB decreased USP22 transcriptional activation and endogenous expression, whereas CREB overexpression did not affect transcriptional levels. Furthermore, USP22 promoter activity and expression were decreased by inhibiting PKA with H-89, but were not responsive to forskolin induction. All of these results demonstrate that PKA/CREB is involved in the regulation of constitutive promoter activity of the USP22 gene.
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xiong
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Zhou
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: The Maternal and Child Health Hospital of Jiujiang City, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
mesh_terms: D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005576:Colforsin / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D013449:Sulfonamides / Q000494:pharmacology; D013869:Thiolester Hydrolases / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D043222:Ubiquitin Thiolesterase
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D013449:Sulfonamides; D005576:Colforsin; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide