Thyroid hormone promotes serine phosphorylation of p53 by mitogen-activated protein kinase

A. Shih, H. Y. Lin, F. B. Davis, P. J. Davis

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108 引文 斯高帕斯(Scopus)

摘要

L-Thyroxine (T 4) nongenomically promotes association of mitogen-activated protein kinase (MAPK) and thyroid hormone receptor TRβ1 (TR) in the cell nucleus, leading to serine phosphorylation of the receptor. The oncogene suppressor protein, p53, is serine phosphorylated by several kinases and is known to interact with TRβ1. We studied whether association of p53 and TR is modulated by T 4 and involves serine phosphorylation of p53 by MAPK. TR-replete 293T human kidney cells were incubated with a physiological concentration of T 4 for 10-90 min. Nuclear fractions were immunoprecipitated and the resulting proteins separated and immunoblotted for co-immunoprecipitated proteins. Activated MAPK immunoprecipitates of nuclei from T 4-treated cells accumulated p53 in a time-dependent manner; T 4 and T 4-agarose were more effective than T 3. T 4-induced nuclear complexing of p53 and MAPK was inhibited by PD 98059 (PD) and U0126, two MAPK kinase (MEK) inhibitors, and was absent in cells treated with MEK antisense oligonucleotide and in dominant negative Ras cells. T 4 also caused nuclear co-immunoprecipitation of TRβ1 and p53, an effect also inhibited by PD. Nuclear complexing of p53 and MAPK also occurred in HeLa cells, which lack functional TR. Constitutively activated MAPK caused phosphorylation of a recombinant p53-GST fusion protein in vitro; thus, p53 is a substrate for MAPK. An indicator of p53 transcriptional activity, accumulation of the immediate - early gene product, c-Jun, was inhibited by T 4. This T 4 effect was reversed by PD, indicating that the transcriptional activity of p53 was altered by T 4-directed MAPK-p53 interaction.
原文英語
頁(從 - 到)2870-2878
頁數9
期刊Biochemistry
40
發行號9
DOIs
出版狀態已發佈 - 三月 6 2001
對外發佈

ASJC Scopus subject areas

  • 生物化學

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