Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1.

BMC Biochemistry (Impact Factor: 1.94). 10/2012; 13(1):20. DOI: 10.1186/1471-2091-13-20
Source: PubMed

ABSTRACT BACKGROUND: STAT1 is an essential transcription factor for interferon-gamma-mediated gene responses. A distinct sumoylation consensus site (psiKxE) 702IKTE705 is localized in the C-terminal region of STAT1, where Lys703 is a target for PIAS-induced SUMO modification. Several studies indicate that sumoylation has an inhibitory role on STAT1-mediated gene expression but the molecular mechanisms are not fully understood. RESULTS: Here, we have performed a structural and functional analysis of sumoylation in STAT1. We show that deconjugation of SUMO by SENP1 enhances the transcriptional activity of STAT1, confirming a negative regulatory effect of sumoylation on STAT1 activity. Inspection of molecular model indicated that consensus site is well exposed to SUMOconjugation in STAT1 homodimer and that the conjugated SUMO moiety is directed towards DNA, thus able to form a sterical hindrance affecting promoter binding of dimeric STAT1. In addition, oligoprecipitation experiments indicated that sumoylation deficient STAT1 E705Q mutant has higher DNA-binding activity on STAT1 responsive gene promoters than wildtype STAT1. Furthermore, sumoylation deficient STAT1 E705Q mutant displayed enhanced histone H4 acetylation on interferon-gamma-responsive promoter compared to wild-type STAT1. CONCLUSIONS: Our results suggest that sumoylation participates in regulation of STAT1 responses by modulating DNA-binding properties of STAT1.

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