PKA/CREB regulates the constitutive promoter activity of the USP22 gene

Xiong,Jianjun; Zhou,Xiaoou; Gong,Zhen; Wang,Ting; Zhang,Chao; Xu,Xiaoyuan; Liu,Jianyun; Li,Weidong

doi:10.3892/or.2015.3740

PKA/CREB regulates the constitutive promoter activity of the USP22 gene

Authors:
- Jianjun Xiong
- Xiaoou Zhou
- Zhen Gong
- Ting Wang
- Chao Zhang
- Xiaoyuan Xu
- Jianyun Liu
- Weidong Li
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Affiliations: College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China, The Maternal and Child Health Hospital of Jiujiang City, Jiujiang, Jiangxi 332000, P.R. China, Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
Published online on: January 20, 2015 https://doi.org/10.3892/or.2015.3740
Pages: 1505-1511

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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.

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