Prothymosin-α enhances phosphatase and tensin homolog expression and binds with tripartite motif-containing protein 21 to regulate Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling in human bladder cancer

Yuh Shyan Tsai, Yeong Chin Jou, Hsin Tzu Tsai, Ai Li Shiau, Chao Liang Wu, Tzong Shin Tzai

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

Prothymosin-α (PTMA) is a small, acidic protein that is usually transported into the nucleus and involves many cellular and immunological functions. Previous studies demonstrated that aberrant location of PTMA expression exists in human bladder cancer, but the role of PTMA protein expression remains elusive. In this study, we created ectopic nuclear or cytoplasmic PTMA expression in human bladder cancer cells by infecting lentiviruses carrying wild type or deleted nuclear localization signal of the PTMA gene. The in vivo tumorigenesis assay showed PTMA protein with deleted nuclear localization signal promotes J82 xenograft tumor growth in mice and shortens their survival more so than the wild type. Chromatin immunoprecipitation showed that wild-type PTMA protein binds to the PTEN promoter and enhances phosphatase and tensin homolog (PTEN) expression. Through immunoblot proteomics and in vivo ubiquitination studies, PTMA protein can bind with tripartite motif-containing protein 21 (TRIM21) and block its ubiquitination. Also, TRIM21 can downregulate both forms of PTMA protein. In human bladder tumors, loss of nuclear PTMA expression was an unfavorable prognostic indicator for shorter disease-free survival (hazard ratio, 1.54; P = 0.009). Our data support that nuclear PTMA protein serves as a tumor suppressor in bladder cancer through upregulating PTEN and orchestrating TRIM21 for the regulation of Nrf2 signaling.

原文English
頁(從 - 到)1208-1219
頁數12
期刊Cancer Science
110
發行號4
DOIs
出版狀態Published - 2019 四月

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

指紋 深入研究「Prothymosin-α enhances phosphatase and tensin homolog expression and binds with tripartite motif-containing protein 21 to regulate Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling in human bladder cancer」主題。共同形成了獨特的指紋。

引用此