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J. Biol. Chem., Vol. 280, Issue 15, 14492-14498, April 15, 2005

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Differential Regulation of c-Jun-dependent Transcription by SUMO-specific Proteases^*

Jinke Cheng, Neil D. Perkins¶, and Edward T. H. Yeh||

From the Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, Research Center for Cardiovascular Diseases, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas-Houston Health Science Center, Houston, Texas 77030, and ^¶Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, United Kingdom

c-Jun is a transcription factor that plays an important role in regulating cell growth, apoptosis, differentiation, and transformation. The transcriptional activity of c-Jun can be regulated by both phosphorylation and sumoylation. It has also been shown that c-Jun transcription can be regulated by SuPr-1, an alternatively spliced form of SUMO-specific protease 2 (SENP2). However, the ability of SuPr-1 to enhance c-Jun transcription is dependent on promyelocytic leukemia but is independent of the desumoylation activity of SuPr-1. Here, we show that SUMO-specific protease 1 (SENP1) also markedly enhances the transcription activity of c-Jun. The action of SENP1 on c-Jun transcription is independent of the sumoylation and phosphorylation status of c-Jun but is critically dependent on the desumoylation activity of SENP1. We further show that p300 is essential for SENP1 to enhance c-Jun-dependent transcription because SENP1 can desumoylate the CRD1 domain of p300, thereby releasing the cis-repression of CRD1 on p300. Thus, two SUMO-specific proteases regulate c-Jun-dependent transcription through entirely different mechanisms.

Received for publication, October 27, 2004 , and in revised form, February 1, 2005.

^* This work was supported in part by National Institutes of Health Grant RO1 CA 80089 (to E. T. H. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Cardiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 449, Houston, TX 77030. Tel.: 713-792-6242; Fax: 713-745-1942; E-mail: etyeh{at}mdanderson.org.

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