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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
Cancer science | 2019

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.

Pubmed ID: 30719818

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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on March 17, 2022. An integrated software suite for functional analysis of experimental data. The scope of data types includes microarray and SAGE gene expression, SNPs and CGH arrays, proteomics, metabolomics, pathway analysis, Y2H and other custom interactions. MetaCore is based on a proprietary manually curated database of human protein-protein, protein-DNA and protein compound interactions, metabolic and signaling pathways and the effects of bioactive molecules in gene expression.

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