Abstract
p53, a tumor suppressor and transcription factor, is a critical modulator in the cellular response to stress. Exposure of glutathione-deficient GCS-2 cells to arsenite significantly phosphorylated and stabilized p53. In addition, p53 transcriptionally repressed Hsp90β gene expression. Mutation analysis revealed a p53 binding site in the 5′ flanking region responsible for the regulation of Hsp90β gene. Electrophoretic mobility shift assay showed that p53 is bound to Hsp90β promoter region. ATM kinase, a major determinant in the modulation of p53 specifically affected its phosphorylation at Ser-15. ATM kinase-mediated phosphorylation of p53 is regulated through phosphorylation of Chk2. Down-regulation of ATM and Chk2 by their small interfering RNAs (siRNAs) attenuated the arsenite-induced phosphorylation of p53 and restored Hsp90β mRNA levels. Taken together, these findings suggest that arsenite acts through ATM and Chk2 to induce phosphorylation of p53. This results in the transcriptional repression of Hsp90β, under GSH-deficient conditions which may play a role in arsenic-mediated pathogenesis.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
