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Sci. STKE, 1 May 2001
Vol. 2001, Issue 80, p. tw8
[DOI: 10.1126/stke.2001.80.tw8]


Transcription Kicked Out by Phosphorylation

AFX, a member of the forkhead family of transcription factors, is inhibited by growth factor signaling through the activation of protein kinase B (PKB), which phosphorylates AFX leading to its redistribution from nucleus to cytosol. In cells treated with insulin, activated PKB was identified in the nucleus. AFX became phosphorylated (AFX-P) in response to insulin, even when nuclear export was inhibited pharmacologically with leptomycin B, suggesting that PKB in the nucleus is responsible for AFX phosphorylation. However, inhibition of nuclear export suppressed inhibition of AFX-activated reporter gene expression in response to insulin, suggesting that the redistribution of AFX, not phosphorylation per se, is responsible for regulation of AFX activity. AFX and AFX-P interacted with the nuclear export receptor Crm1 and were shuttled out of the nucleus. However, phosphorylation of AFX decreases nuclear import. The authors suggest that growth factor signaling leads to nuclear phosphorylation of AFX, which allows nuclear export but prevents import, possibly because of the interaction of AFX-P with cytosolic 14-3-3 proteins.

A. M. Brownawell, G. J. P. L. Kops, I. G. Macara, B. M. T. Burgering, Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX. Mol. Cell. Biol. 21, 3534-3546 (2001). [Abstract] [Full Text]

Citation: Kicked Out by Phosphorylation. Sci. STKE 2001, tw8 (2001).

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