p38 mitogen‑activated protein kinase inhibits USP22 transcription inHeLa cells

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

来源：Biomedical Reports, 2015, 3(4): 461-467.

DOI：10.3892/br.2015.450

• UPS22
• p38 mitogen-activated protein kinase
• transcription

Elevated expression of ubiquitin‑specific processing enzyme 22 (USP22) wasidentified in multiple types of human cancers, and was correlated with tumorigenesisand progression. Despite an increase in the numbers of studies in the physiologicalfunction of USP22, little is known regarding the regulation of its expression.The 5' flanking sequence of the USP22 gene was recently characterized. In thepresent study, USP22 transcription was regulated by p38 mitogen‑activated proteinkinase (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, resultedin a 40% decrease in USP22 mRNA, while the dominant negative MKK6 increased thetranscription level of the USP22, similar to SB203580. Dual luciferase reportassays showed that mutations of the Sp1 binding site ahead of the transcriptionstart site abolished the promoting effect of the USP22 promoter by ...