PIAS proteins promote SUMO-1 conjugation to STAT1.
Signal transducer and activator of transcription 1 (STAT1) is a critical mediator of interferon-gamma (IFN-gamma)-induced transcription that is regulated through posttranslational modifications and through transacting proteins such as protein inhibitor of activated STAT1 (PIAS1). PIAS proteins have been shown to function as E3-type small ubiquitin-like modifier (SUMO) ligases, and sumoylation has been identified as a modulatory mechanism for several transcription factors. Here we show that STAT1 is subject to SUMO-1 modification, and sumoylation occurs in vivo and in vitro at a single, evolutionary conserved amino acid residue Lys703. Members of the PIAS family of proteins were found to strongly stimulate sumoylation of STAT1. Furthermore, activation of STAT1 by IFN-gamma or pervanadate induced SUMO-1 conjugation. Mutation of Lys703 in STAT1 resulted in increased IFN-gamma-mediated transactivation, suggesting a negative regulatory function for sumoylation. These results indicate that STAT1 is covalently modified by SUMO-1 in cytokine signaling and that PIAS proteins promote SUMO-1 conjugation to STAT1.
Ungureanu
Daniela
D
Institute of Medical Technology, University of Tampere, Lenkkeilijankatu 8, FIN-33014, Tampere, Finland.
Vanhatupa
Sari
S
Kotaja
Noora
N
Yang
Jie
J
Aittomaki
Saara
S
Jänne
Olli A
OA
Palvimo
Jorma J
JJ
Silvennoinen
Olli
O
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009154:Mutation; D050828:Protein Inhibitors of Activated STAT; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000502:physiology*; D050794:STAT1 Transcription Factor; D025842:SUMO-1 Protein / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014638:Vanadates / Q000494:pharmacology
D004268:DNA-Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D025842:SUMO-1 Protein; D015534:Trans-Activators; C076715:pervanadate; D014638:Vanadates; D007371:Interferon-gamma