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Molecular and Cellular Biology, July 2002, p. 5222-5234, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5222-5234.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

PIAS Proteins Modulate Transcription Factors by Functioning as SUMO-1 Ligases

Noora Kotaja,1 Ulla Karvonen,1 Olli A. Jänne,1,2 and Jorma J. Palvimo1,3*

Biomedicum Helsinki, Institute of Biomedicine,1 Department of Clinical Chemistry,2 Institute of Biotechnology, University of Helsinki and Helsinki University Central Hospital, FIN-00014 Helsinki, Finland3

Received 6 November 2001/ Returned for modification 26 December 2001/ Accepted 8 April 2002

PIAS (protein inhibitor of activated STAT) proteins interact with and modulate the activities of various transcription factors. In this work, we demonstrate that PIAS proteins x{alpha}, xß, 1, and 3 interact with the small ubiquitin-related modifier SUMO-1 and its E2 conjugase, Ubc9, and that PIAS proteins themselves are covalently modified by SUMO-1 (sumoylated). PIAS proteins also tether other sumoylated proteins in a noncovalent fashion. Furthermore, recombinant PIASx{alpha} enhances Ubc9-mediated sumoylation of the androgen receptor and c-Jun in vitro. Importantly, PIAS proteins differ in their abilities to promote sumoylation in intact cells. The ability to stimulate protein sumoylation and the interaction with sumoylated proteins are dependent on the conserved PIAS RING finger-like domain. These functions are linked to the activity of PIASx{alpha} on androgen receptor-dependent transcription. Collectively, our results imply that PIAS proteins function as SUMO-1-tethering proteins and zinc finger-dependent E3 SUMO protein ligases, and these properties are likely to explain their ability to modulate the activities of various transcription factors.

* Corresponding author. Mailing address: Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland. Phone: 358-9-191 25291. Fax: 358-9-191 25302. E-mail: jorma.palvimo{at}helsinki.fi.

Molecular and Cellular Biology, July 2002, p. 5222-5234, Vol. 22, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.14.5222-5234.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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