LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest

Inactivating mutations in the serine-threonine kinase LKB1 (STK11) are foun d in most patients with Peutz-Jeghers syndrome; however the function of LKB 1 is unknown. We found that TK I binds to and regulates brahma-related gene I (Brg1), an essential component of chromatin remodeling complexes. The as sociation requires the N terminus of LKB1 and the helicase domain of Brg1 a nd LKB1 stimulates the ATPase activity of Brg1. Brg1 expression in SW13 cel ls 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 r equired for Brg1-dependent growth arrest. The inability of mutants of LKB1 to mediate Brg1-dependent growth arrest may explain the manifestations of P eutz-Jeghers syndrome.