55193

PBRM1

BAF180|PB1;polybromo 1;PBRM1;polybromo 1

BRG1-associated factor 180|polybromo-1D|protein polybromo-1

3p21

protein-coding

Count: 3; Pubmed_search,Generif,UniProt

Screening for tumor suppressor genes in breast cancer revealed multiple truncating mutations of PB1, which encodes the BAF180 subunit of the PBAF chromatin remodeling complex. mutation was associated with loss of heterozygosity of the wild-type allele. BAF180 complementation of BAF180-mutant tumor cells caused G(1) arrest that was dependent on increased expression of the cyclin/cyclin-dependent kinase inhibitor p21/WAF1/CIP1. Endogenous wild-type BAF180 bound to the p21 promoter and was required for proper p21 expression and G(1) arrest after transforming growth factor-beta and gamma-radiation treatment. BAF180 thus functions on two tumor suppressor signaling pathways as a physiologic mediator of p21 expression. We conclude that BAF180 suppresses tumorigenesis, at least in part, through its ability to regulate p21.

BAF180 encoding a subunit of the human SWI/SNF chromatin remodeling complex maps to 3p21, in a region where frequent allele loss has been detected in lung cancer. BAF180 can be mutated and has tumor suppressing properties in breast cancer. In addition, another member of this complex, hSNF5/INI1, is a known tumor suppressor gene (TSG) for malignant rhabdoid and childhood central nervous system tumors. Thus, BAF180 is a strong candidate TSG for lung cancer. The objective of this study was to determine whether BAF180 mRNA or protein expression was inactivated or abnormal in lung cancers to prompt detailed DNA promoter methylation or mutational analyses. In 30 non-small-cell and 26 small-cell lung cancer cell lines, most of which had 3p21 allele loss, BAF180 mRNA and protein expression were evaluated by RT-PCR using three sets of primers and Western blotting using two anti-BAF180 antibodies. In all cases, BAF180 was expressed and no abnormal size BAF180 protein was detected. Finally, we found no amino-acid sequence coding mutations in five non-small-cell and five small-cell lung cancer cell lines, while we did find a new splicing isoform of BAF180 (AY281068). We conclude that abnormalities of BAF180 are not frequently involved in the pathogenesis of lung cancer.

The bromodomain is suggested as a chromatin-targeting domain involved in regulation of gene expression and chromatin structure. We here report the cDNA cloning of the human polybromo-1 (hPB1) gene that encodes a 1634-amino acid polypeptide containing six bromodomains. The hPB1 polypeptide shows 91% identity to the previously identified chicken polybromo-1 with conservation of the bromodomains and other characteristic features. Northern blot analysis detected the ubiquitous expression of hPB1 mRNA in a variety of human tissues. Four alternative splicings were found within the hPB1 coding region: three making in-frame deletions and one resulting in a C-terminal truncation. The hPB1 gene is located on chromosome 3p21, where the tumor suppressor genes for breast, lung and kidney cancers have been mapped.