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	Jianjun Xiong, Xiaoou Zhou, Zhen Gong, Ting Wang, Chao Zhang, Xiaoyuan Xu, Jianyun Liu, Weidong Li
Journal	Oncology reports (Oncol Rep) Vol. 33 Issue 3 Pg. 1505-11 (Mar 2015) ISSN: 1791-2431 [Electronic] Greece
PMID	25607216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CREB1 protein, human Cyclic AMP Response Element-Binding Protein Isoquinolines Protein Kinase Inhibitors RNA, Small Interfering Sulfonamides Colforsin Thiolester Hydrolases Ubiquitin Thiolesterase Usp22 protein, human N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
Topics	Binding Sites (genetics) Cell Line, Tumor Chromatin Immunoprecipitation Colforsin (metabolism) Cyclic AMP Response Element-Binding Protein (biosynthesis, genetics, metabolism) HeLa Cells Hep G2 Cells Humans Isoquinolines (pharmacology) Mutation (genetics) Neoplasms (genetics, pathology) Promoter Regions, Genetic (genetics) Protein Kinase Inhibitors (pharmacology) RNA Interference RNA, Small Interfering Sulfonamides (pharmacology) Thiolester Hydrolases (genetics) Transcriptional Activation (genetics) Ubiquitin Thiolesterase

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