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

被引：108

作者：

Marignani, PA ^{[1
]}

Kanai, F

Carpenter, CL

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA

[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Cell Biol,Div Signal Transduct, Boston, MA 02215 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2001年 / 276卷 / 35期

关键词：

D O I：

10.1074/jbc.C100207200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 TK I binds to and regulates brahma-related gene I (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.

引用

页码：32415 / 32418

页数：4

共 45 条

[1] LKB1 somatic mutations in sporadic tumors [J].

Avizienyte, E ;

Loukola, A ;

Roth, S ;

Hemminki, A ;

Tarkkanen, M ;

Salovaara, R ;

Arola, J ;

Bützow, R ;

Husgafvel-Pursiainen, K ;

Kokkola, A ;

Järvinen, H ;

Aaltonen, LA .

AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (03) :677-681

[2] BRCA1 is associated with a human SWI/SNF-related complex: Linking chromatin remodeling to breast cancer [J].

Bochar, DA ;

Wang, L ;

Beniya, H ;

Kinev, A ;

Xue, YT ;

Lane, WS ;

Wang, WD ;

Kashanchi, F ;

Shiekhattar, R .

CELL, 2000, 102 (02) :257-265

[3] A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes [J].

Bultman, S ;

Gebuhr, T ;

Yee, D ;

La Mantia, C ;

Nicholson, J ;

Gilliam, A ;

Randazzo, F ;

Metzger, D ;

Chambon, P ;

Crabtree, G ;

Magnuson, T .

MOLECULAR CELL, 2000, 6 (06) :1287-1295

[4] 2 HUMAN HOMOLOGS OF SACCHAROMYCES-CEREVISIAE SW12/SNF2 AND DROSOPHILA-BRAHMA ARE TRANSCRIPTIONAL COACTIVATORS COOPERATING WITH THE ESTROGEN-RECEPTOR AND THE RETINOIC ACID RECEPTOR [J].

CHIBA, H ;

MURAMATSU, M ;

NOMOTO, A ;

KATO, H .

NUCLEIC ACIDS RESEARCH, 1994, 22 (10) :1815-1820

[5] Identification of a novel mRNA species of the LKB1/STK11 Peutz-Jeghers serine/threonine kinase [J].

Churchman, M ;

Dowling, B ;

Tomlinson, IPM .

DNA SEQUENCE, 1999, 10 (4-5) :255-+

[6] LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo [J].

Collins, SP ;

Reoma, JL ;

Gamm, DM ;

Uhler, MD .

BIOCHEMICAL JOURNAL, 2000, 345 :673-680

[7] BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation [J].

DiRenzo, J ;

Shang, YF ;

Phelan, M ;

Sif, S ;

Myers, M ;

Kingston, R ;

Brown, M .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (20) :7541-7549

[8] THE RETINOBLASTOMA PROTEIN AND BRG1 FORM A COMPLEX AND COOPERATE TO INDUCE CELL-CYCLE ARREST [J].

DUNAIEF, JL ;

STROBER, BE ;

GUHA, S ;

KHAVARI, PA ;

ALIN, K ;

LUBAN, J ;

BEGEMANN, M ;

CRABTREE, GR ;

GOFF, SP .

CELL, 1994, 79 (01) :119-130

[9] Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome [J].

Entius, MM ;

Keller, JJ ;

Westerman, AM ;

van Rees, BP ;

van Velthuysen, MLF ;

de Goeij, AFPM ;

Wilson, JHP ;

Giardiello, FM ;

Offerhaus, GJA .

JOURNAL OF CLINICAL PATHOLOGY, 2001, 54 (02) :126-131

[10] Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome [J].

Esteller, M ;

Avizienyte, E ;

Corn, PG ;

Lothe, RA ;

Baylin, SB ;

Aaltonen, LA ;

Herman, JG .

ONCOGENE, 2000, 19 (01) :164-168

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