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Molecular and Cellular Biology, February 2005, p. 1549-1559, Vol. 25, No. 4
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.4.1549-1559.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role for SUMO Modification in Facilitating Transcriptional Repression by BKLF{dagger}

José Perdomo,1,{ddagger} Alexis Verger,1,{ddagger} Jeremy Turner,1,§ and Merlin Crossley1*

School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New South Wales, Australia1

Received 3 November 2004/ Returned for modification 20 November 2004/ Accepted 14 December 2004

Small ubiquitin-like modifier (SUMO) is a protein moiety that is ligated to lysine residues on a variety of target proteins. Many known SUMO substrates are transcription factors or coregulators of transcription, and in most cases, modification with SUMO leads to the attenuation of transcriptional activation. We have examined basic Krüppel-like factor/Krüppel-like factor 3 (BKLF), a zinc finger transcription factor that is known to function as a potent transcriptional repressor. We show that BKLF recruits the E2 SUMO-conjugating enzyme Ubc9 and can be modified by the addition of SUMO-1 in vitro and in vivo. The SUMO E3 ligases PIAS1, PIAS{gamma}, PIASx{alpha}, and PIASxß but not Pc2 enhance the sumoylation of BKLF. Site-directed mutagenesis identified two lysines (K10 and K197) of BKLF as the sumoylation sites. Sumoylation does not detectably affect DNA binding by BKLF, but mutation of the sumoylation sites reduces transcriptional repression activity. Most interestingly, when mutations preventing sumoylation are combined with an additional mutation that eliminates contact with the C-terminal binding protein (CtBP) corepressor, BKLF becomes an activator of transcription. These results link SUMO modification to transcriptional repression and demonstrate that both recruitment of CtBP and sumoylation are required for full repression by BKLF.

* Corresponding author. Mailing address: School of Molecular and Microbial Biosciences G08, University of Sydney, Sydney, New South Wales 2006, Australia. Phone: 61 2 9351 2233. Fax: 61 2 9351 4726. E-mail: m.crossley{at}mmb.usyd.edu.au.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} J.P. and A.V. contributed equally to this work.

§ Present address: Centre for Thrombosis and Vascular Research, School of Medical Sciences and Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.

Molecular and Cellular Biology, February 2005, p. 1549-1559, Vol. 25, No. 4
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.4.1549-1559.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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