title: p38 mitogen-activated protein kinase inhibitsUSP22transcription in HeLa cells.
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 ofUSP22, little is known regarding the regulation of its expression. The 5' flanking sequence of theUSP22gene was recently characterized. In the present study,USP22transcription was regulated by p38 mitogen-activated protein kinase (MAPK). Treatment of human cervical carcinoma (HeLa) cells with SB203580, an inhibitor of p38 MAPK, enhanced basalUSP22promoter activity and mRNA abundance. Transfection of MAPK kinase 6 (MKK6), an upstream activator of p38 MAPK, resulted in a 40% decrease inUSP22mRNA, while the dominant negative MKK6 increased the transcription level of theUSP22, 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 theUSP22promoter by SB203580. Cisplatin, the activator of p38 MAPK, also suppressedUSP22expression. This suppression was blocked by SB203580. In conclusion, p38 MAPK acts as an upstream negative regulator ofUSP22transcription in HeLa cells.
authors.affiliation: 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.
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: Zhen
authors.initials: Z
authors.lastname: Gong
authors.affiliation: 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.
authors.forename: Xiaou
authors.initials: X
authors.lastname: Zhou
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: H E
authors.initials: HE
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
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
keywords: UPS22; p38 mitogen-activated protein kinase; transcription