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Originally published In Press as doi:10.1074/jbc.C100207200 on July 9, 2001

J. Biol. Chem., Vol. 276, Issue 35, 32415-32418, August 31, 2001
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ACCELERATED PUBLICATION
LKB1 Associates with Brg1 and Is Necessary for Brg1-induced Growth Arrest*

Paola A. MarignaniDagger §, Fumihiko Kanai||, and Christopher L. CarpenterDagger **

From the Departments of Dagger  Medicine and  Cell Biology, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215

Inactivating mutations in the serine-threonine kinase LKB1 (STK11) are found in most patients with Peutz-Jeghers syndrome; however the function of LKB1 is unknown. We found that LKB1 binds to and regulates brahma-related gene 1 (Brg1), an essential component of chromatin remodeling complexes. The association requires the N terminus of LKB1 and the helicase domain of Brg1 and LKB1 stimulates the ATPase activity of Brg1. Brg1 expression in SW13 cells induces the formation of flat cells indicative of cell cycle arrest and senescence. Expression of a kinase-dead mutant of LKB1, SL26, in SW13 cells blocks the formation of Brg1-induced flat cells, indicating that LKB1 is required for Brg1-dependent growth arrest. The inability of mutants of LKB1 to mediate Brg1-dependent growth arrest may explain the manifestations of Peutz-Jeghers syndrome.

* This work was supported in part by Grant GM 54389 from the National Institutes of Health (to C. L. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Ontario Cancer Inst., Princess Margaret Hospital, 610 University Ave., Toronto, Ontario M5G 7M9, Canada. E-mail: marignan@uhnres.utoronto.ca.

|| Present address: Dept. of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

** To whom correspondence should be addressed. E-mail: ccarpent@caregroup.harvard.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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