%0 Journal Article
%T Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1
%A Gr£¿nholm Juha
%A Vanhatupa Sari
%A Ungureanu Daniela
%A V£¿liaho Jouni
%J BMC Biochemistry
%D 2012
%I BioMed Central
%R 10.1186/1471-2091-13-20
%X Background STAT1 is an essential transcription factor for interferon-¦Ã-mediated gene responses. A distinct sumoylation consensus site (¦×KxE) 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 SUMO-conjugation 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 wild-type STAT1. Furthermore, sumoylation deficient STAT1 E705Q mutant displayed enhanced histone H4 acetylation on interferon-¦Ã-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.
%K Signal transduction
%K Transcription factors
%K Sumoylation
%K Signal transducers and activators of transcription (STATs)
%K Interferon
%U http://www.biomedcentral.com/1471-2091/13/20