期刊
CELL CYCLE
卷 9, 期 12, 页码 2442-2455出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.12.12053
关键词
p53; 3 '-> 5 ' exonuclease; dsRNA degradation
类别
Double-stranded RNA (dsRNA) is a biologically active molecule that plays important roles in normal cell growth and function. Accordingly, the cell uses multiple mechanisms to control its level. the tumor suppressor protein p53 possesses intrinsic 3'-> 5' exonuclease activity. the aim of the present study was to elucidate the degradation of dsRNA by the exonuclease activity of p53. the results show that recombinant, purified wtp53 and endogenous protein in cytoplasmic fractions of cells remove nucleotides from 3'-ends of dsRNA. Several lines of evidence support a connection between p53 and dsRNase activity in cytoplasm: (1) this activity parallels the status of endogenous cytoplasmic p53; (2) the endogenous exonuclease displays a similar dsRNA excision profile characteristic for purified wtp53; (3) cytoplasmic fractions of HCT116(p53(+/+)) cells exert higher levels of exonuclease activity compared to those of HCT116(p53(-/-)) cells; (4) transfection of the wtp53, but not exonuclease-deficient mutant p53-R175H into HCt116 (p53(-/-)) cells induced high levels of dsRNase activity in cytoplasm; (5) the accumulation of p53 in cytoplasm following the gamma-irradiation stress stimuli correlates with the increase in the excision of dsRNA and (6) the dsRNA forms a complex with a protein that can be disrupted by an anti-p53 antibody. our data suggest that the degradation of dsRNA by p53 protein may direct either the complete degradation and decrease in the level of dsRNA, or incomplete degradation and the generation of short dsRNA products. the possible roles of p53 dsRNase activity in cytoplasm in the inhibition of translation and induction of cell apoptosis, is discussed.
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