p38 mitogen‑activated protein kinase inhibits USP22 transcription in HeLa cells

Xiong,Jianjun; Gong,Zhen; Zhou,Xiaou; Liu,Jianyun; Jiang,He; Wu,Ping; Li,Weidong

doi:10.3892/br.2015.450

p38 mitogen‑activated protein kinase inhibits USP22 transcription in HeLa cells

Authors:
- Jianjun Xiong
- Zhen Gong
- Xiaou Zhou
- Jianyun Liu
- He Jiang
- Ping Wu
- Weidong Li
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Affiliations: Key Laboratory of Jiangxi Province for the Systems Bio‑Medicine, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China, College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China
Published online on: April 16, 2015 https://doi.org/10.3892/br.2015.450
Pages: 461-467

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Abstract

Elevated expression of ubiquitin‑specific processing enzyme 22 (USP22) was identified in multiple types of human cancers, and was correlated with tumorigenesis and progression. Despite an increase in the numbers of studies in the physiological function of USP22, little is known regarding the regulation of its expression. The 5' flanking sequence of the USP22 gene was recently characterized. In the present study, USP22 transcription was regulated by p38 mitogen‑activated protein kinase (MAPK). Treatment of human cervical carcinoma (HeLa) cells with SB203580, an inhibitor of p38 MAPK, enhanced basal USP22 promoter activity and mRNA abundance. Transfection of MAPK kinase 6 (MKK6), an upstream activator of p38 MAPK, resulted in a 40% decrease in USP22 mRNA, while the dominant negative MKK6 increased the transcription level of the USP22, similar to SB203580. Dual luciferase report assays showed that mutations of the Sp1 binding site ahead of the transcription start site abolished the promoting effect of the USP22 promoter by SB203580. Cisplatin, the activator of p38 MAPK, also suppressed USP22 expression. This suppression was blocked by SB203580. In conclusion, p38 MAPK acts as an upstream negative regulator of USP22 transcription in HeLa cells.

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