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Molecular and Cellular Biology, May 2005, p. 4272-4282, Vol. 25, No. 10
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.10.4272-4282.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
A Small Conserved Surface in SUMO Is the Critical Structural Determinant of Its Transcriptional Inhibitory Properties
Sergey Chupreta,
Sam Holmstrom,
Lalitha Subramanian, and
Jorge A. Iñiguez-Lluhí*
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0632
Received 13 November 2004/
Returned for modification 30 December 2004/
Accepted 16 February 2005
Small ubiquitin-like modifier (SUMO) modification of sequence-specific transcription factors has profound regulatory consequences. By providing an intrinsic inhibitory function, SUMO isoforms can suppress transcriptional activation, particularly at promoters harboring multiple response elements. Through a comprehensive structure-function analysis, we have identified a single critical sector along the second beta sheet and the following alpha helix of SUMO2. This distinct surface is defined by four basic residues (K33, K35, K42, R50) that surround a shallow pocket lined by aliphatic (V30, I34) and polar (T38) residues. Substitutions within this area specifically and dramatically affected the ability of both SUMO2 and SUMO1 to inhibit transcription and revealed that the positively charged nature of the key basic residues is the main feature responsible for their functional role. This highly conserved surface accounts for the inhibitory properties of SUMO on multiple transcription factors and promoter contexts and likely defines the interaction surface for the corepressors that mediate the inhibitory properties of SUMO.
* Corresponding author. Mailing address: Department of Pharmacology, University of Michigan Medical School, 1301 MSRBIII, Ann Arbor, MI 48109-0632. Phone: (734) 625-6565. Fax: (734) 763-4450. E-mail: iniguez{at}umich.edu.
S.C. and S.H. contributed equally to this work.
Molecular and Cellular Biology, May 2005, p. 4272-4282, Vol. 25, No. 10
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.10.4272-4282.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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Copyright © 2005 by the American Society for Microbiology. All rights reserved.