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Sugary STAT Recruits CBP

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Science's STKE  03 Feb 2004:
Vol. 2004, Issue 218, pp. tw38-TW38
DOI: 10.1126/stke.2182004TW38

Posttranslational modification by N-acetylglucosamine (O-GlcNAc) has been reported for several proteins involved in the regulation of transcription. Gewinner et al. show that several members of the STAT family of transcription factors (STAT5, STAT1, STAT3, and STAT6) were modified by the addition of O-GlcNAc in response to cytokine, hormone, or growth factor stimulation of HC11 mouse mammary epithelial cells (different STATs are activated by different ligands). STAT5a glycosylation was explored in more detail. Glycosylation was stimulated by prolactin treatment of the cells, and glycosylated STAT5a was more abundant in the nucleus than in the cytoplasm. Glycosylation of STAT5 did not influence tyrosine or serine phosphorylation or DNA-binding ability. Mutation of Thr92 substantially diminished glycosylation of STAT5, although it did not impair phosphorylation or DNA binding. The T92A mutant did not stimulate reporter gene expression in transfected cells. In vitro, STAT5 only interacted with the transcriptional coactivator CBP when glycosylated. However, glycosylation status did not affect STAT5's interaction with several other cofactors. Thus, dynamic glycosylation may contribute to the activation of STAT-regulated genes by controlling interaction with a subset of cofactors.

C. Gewinner, G. Hart, N. Zachara, R. Cole, C. Beisenherz-Huss, B. Groner, The coactivator of transcription CREB-binding protein interacts preferentially with the glycosylated form of Stat5. J. Biol. Chem. 279, 3563-3572 (2004). [Abstract] [Full Text]

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