Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from tumors is altered compared to wild-type p53
- National Cancer Institute, Bethesda, MD (United States)
- Brookhaven National Laboratory, Upton, NY (United States)
- Thomas Jefferson Univ., Philadelphia, PA (United States)
The product of the p53 gene suppresses cell growth and plays a critical role in suppressing development of human tumors. p53 protein binds DNA, activates transcription, and can be phosphorylated at N- and C-terminal sites. Previously, wild-type p53 was shown to be hyperphosphorylated compared to mutant p53 during p53-mediated growth arrest in vivo. Here we show that Ser-15 and Ser-9 in the N-terminal transactivation domain of wild-type human p53 are phosphorylated in vivo in cells derived from the human glioblastoma line T98G. In [IIe[sup 237]] p53 and [Ala[sup 143]] p53, two natural p53 mutants from human tumors that are defective for activation of transcription, phosphorylation at Ser-15 was reduced and phosphorylation at Ser-392 was increased compared to wild-type p53. No change was observed at Ser-9. [His[sup 273]] p53, a third mutant, had a phosphorylation state similar to that of wild-type p53. We suggest that phosphorylation of Ser-15 may depend on the ability of p53 to adopt a wild-type conformation and may contribute to p53's ability to block cell growth. 56 refs., 2 figs., 1 tab.
- OSTI ID:
- 6281962
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 90:13; ISSN PNASA6; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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