Akting Upon Nurr77

Science's STKE  03 Apr 2001:
Vol. 2001, Issue 76, pp. tw5
DOI: 10.1126/stke.2001.76.tw5

The transcription factor Nurr77, an orphan nuclear receptor, can promote apoptosis in immature thymocytes. Nurr77-dependent transcription is partially controlled by phosphorylation of Ser350, which reduces the DNA binding activity of Nurr77. Pekarsky et al. observed that Akt, a serine-threonine kinase that lies in the phosphatidylinositol 3' kinase (PI3K)-dependent antiapoptotic pathway, coprecipitated with Nurr77 (in cells transfected with Akt and Nurr77), and phosphorylated Nurr77 on Ser350 in vitro and in vivo. Further experiments confirmed that Akt-mediated phosphorylation decreased Nurr77-mediated gene expression as measured by gene reporter assays. These data suggest that one way Akt regulates antiapoptotic effects is by preventing the activation of Nurr77-dependent gene expression.

Y. Pekarsky, C. Hallas, A. Palamarchuk, A. Koval, F. Bullrich, Y. Hirata, R. Bichi, J. Letofsky, C. M. Croce, Akt phosphorylates and regulates the orphan nuclear receptor Nurr77. Proc. Natl. Acad. Sci. U.S.A. 98, 3690-3694 (2001). [Abstract] [Full Text]