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

Juha Grönholm, Sari Vanhatupa, Daniela Ungureanu, Jouni Väliaho, Tuomo Laitinen, Jarkko Valjakka, Olli Silvennoinen

    Research output: Contribution to journalArticleScientificpeer-review

    22 Citations (Scopus)

    Abstract

    Background: STAT1 is an essential transcription factor for interferon-γ-mediated gene responses. A distinct sumoylation consensus site (ψKxE) 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-γ- 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.

    Original languageEnglish
    Article number20
    JournalBMC BIOCHEMISTRY
    Volume13
    Issue number1
    DOIs
    Publication statusPublished - 2012
    Publication typeA1 Journal article-refereed

    Keywords

    • Interferon
    • Signal transducers and activators of transcription (STATs)
    • Signal transduction
    • Sumoylation
    • Transcription factors

    Publication forum classification

    • Publication forum level 1

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