mercredi 29 février 2012

Mutated genes in cancer (53) – SMARCA4

SMARCA4 (also known as BRG)

In databases:

● Entrez ( 6597 or SMARCA4
● Ensembl ( ENSG00000127616
● UniProt ( P51532
● GeneCards ( SMARCA4
● HGNC ( 11100 or SMARCA4
● Enzyme Number (IUBMB): EC 3.6.1.-, EC 3.6.4.-

Gene locus:


Protein name:

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4

Protein Size:

1647 amino acids; about 185 kDa


The SMARCA4 harbors the ATPase activity required for the chromatin remodeling activity of the SWI/SNF complex. This complex uses the energy of ATP hydrolysis to modify the interactions among histones leading to modifications of the chromatin structure and to the regulation of gene expression. The SWI/SNF complex plays a role in differentiation, development and cell cycle control. SMARCA4 binds to or it is related to important tumor suppressor proteins, including BRCA2, LKB1, RB and FANCA. Moreover, the SWI/SNF complex has been shown to modulate the transcriptional activity of steroid receptors (e.g. glucocorticoids receptors, retinoic acid receptors, androgen and estrogen receptors), CMYC and RB. SMARCA4 acts as a tumor suppressor

Cancer-related alterations

SMARCA4 germline mutations have not been reported so far.
SMARCA4 somatic mutations have been identified in a significant proportion of tumors and cancer cell lines including those from the lung, prostate, breast, pancreas and colon. Thus, SMARCA4 is a bona fide tumor suppressor gene and is clearly implicated in cancer development. The type of mutations commonly observed include nonsense, missense and large deletions. No specific mutation hot spot has been described.

References (open access):

BRG1 and LKB1: tales of two tumor suppressor genes on chromosome 19p and lung cancer. Rodriguez-Nieto S, Sanchez-Cespedes M. Carcinogenesis. 2009 Apr;30(4):547-54.

BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression. Cohen SM, Chastain PD 2nd, Rosson GB, Groh BS, Weissman BE, Kaufman DG, Bultman SJ. Nucleic Acids Res. 2010 Nov 1;38(20):6906-19.

The chromatin remodelling factor BRG1 is a novel binding partner of the tumor suppressor p16INK4a. Becker TM, Haferkamp S, Dijkstra MK, Scurr LL, Frausto M, Diefenbach E, Scolyer RA, Reisman DN, Mann GJ, Kefford RF, Rizos H. Mol Cancer. 2009 Jan 16;8:4.

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