LKB1 Associates with Brg1 and Is Necessary for Brg1-induced Growth Arrest

Paola A. Marignani, Fumihiko Kanai, Christopher L. Carpenter

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

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 Brgl 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.

Original languageEnglish
Pages (from-to)32415-32418
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number35
DOIs
Publication statusPublished - Aug 31 2001
Externally publishedYes

ASJC Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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