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p53-related Protein Kinase-binding Protein CGI-121
Ai-Wu Tan, Yao-Zhou Zhang*
Institute of Biochemistry, College of Life Science, Zhejiang Sci-Tec University, Hangzhou 310018, China
Abstract: A novel p53-related protein kinase (PRPK) binding protein CGI-121 was isolated from human testis cDNA library by the yeast two-hybrid screening using PRPK as the bait. The recombinant CGI-121 could suppress phosphorylation of p53 at Ser15 by PRPK in vitro; the unphosphorylated p53 was degraded by ubiquitin-proteasome pathway, which lead to cell proliferation or tumorigenesis; However, overexpression of recombinant CGI-121 in vivo had no remarkable impact on inhibition of p53 phosphorylation by PRPK. At the same time, the suppressor CGI-121 was screened from the cdc13-1 mutant of Saccharomyces cerevisiae by Michael Downey et al.. CGI-121 was a component of the KEOPS complex, and KEOPS is a novel conserved complex in eukaryotes, which could promoting telomere uncapping and telomere elongation. The CGI-121 mutants could suppress ssDNA accumulation and shorten length of telomeres in the cdc13-1 strain, and CGI-121 might promote telomere uncapping in budding yeast under the conditions of telomere dysfunction. However, the expression and regulation mechanism of CGI-121 and the roles acting in the PRPK pathway and the KEOPS complex are unclear up to now.