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J. Biol. Chem., Vol. 283, Issue 26, 18124-18134, June 27, 2008

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SUMO Conjugation to the Matrix Attachment Region-binding Protein, Special AT-rich Sequence-binding Protein-1 (SATB1), Targets SATB1 to Promyelocytic Nuclear Bodies Where It Undergoes Caspase Cleavage^*

Joseph-Anthony T. Tan, Yujie Sun¹, Jing Song^¶2, Yuan Chen, Theodore G. Krontiris, and Linda K. Durrin³

From the Division of Molecular Medicine, Division of Immunology, and ^¶Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope Medical Center, Duarte, California 91010

SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs). To investigate the role of SATB1 in cellular events, we performed a yeast two-hybrid screen that identified SUMO-1, Ubc9, and protein inhibitor of activated STAT (PIAS) family members as SATB1 interaction partners. These proteins, working in concert, enhanced SUMO conjugation to lysine-744 of SATB1. Overexpression of SUMO or PIAS in Jurkat cells, which express high levels of endogenous SATB1, exhibited enhanced caspase cleavage of this MAR-associating protein. Sumoylation-deficient SATB1 (SATB1(K744R)) failed to display the characteristic caspase cleavage pattern; however, fusion of SUMO in-frame to SATB1(K744R) restored cleavage. A SUMO-independent interaction of inactive caspase-6 and SATB1 was noted. A subset of total cellular SATB1 localized into promyelocytic leukemia nuclear bodies where enhanced SATB1 cleavage was detected subsequent to caspase activation. These results reveal a novel sumoylation-directed caspase cleavage of this key regulatory molecule. The role of regulated proteolysis of SATB1 may be to control transcription in immune cells during normal cell functions or to assist in efficient and rapid clearance of nonfunctional or potentially damaging immune cells.

Received for publication, January 22, 2008 , and in revised form, March 19, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants CA51985 (to T. G. K.) and CA94595 (to Y. C.) from the United States Public Health Service and Grant K01 CA097283-02 (to L. K. D.) from the National Cancer Institute. This work was also supported by the Beckman Research Institute of the City of Hope National Medical Center and by Grant 30371592 from the National Nature Science Foundation of China (to Y. S.). 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.

¹ Present address: Dept. of Cell Biology and Medical Genetics, Nanjing Medical University Nanjing Han Kou Road 140, Nanjing 210029, China.

² Present address: CBR Inst. for Biomedical Research and Dept. of Pathology, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115.

³ To whom correspondence should be addressed: Div. of Molecular Medicine, Beckman Research Inst., 1500 E. Duarte Rd., Duarte, CA 91010. Tel.: 626-256-4673, Ext. 62197; Fax: 626-301-8862; E-mail: ldurrin{at}coh.org.

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