Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a protein that in humans is encoded by the PBRM1 gene.[5][6][7]
Human PBRM1 is one of three unique components of the SWI/SNF-B (PBAF) chromatin-remodeling complex, which contains at least SMARCA4/BRG1, SMARCB1/SNF5/INI1/BAF47, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, and actin.[8][9]
Chicken PB1 possesses 5 bromodomains, 2 bromo-adjacent homology (BAH) domains, and 1 truncated high-mobility group (HMG) motif. cPB1 is also homologous to yeast Rsc1, Rsc2, and Rsc4, essential proteins that are required for cell cycle progression through mitosis.[5]
PBRM1 is thought to be a tumor suppressor gene in many cancer subtypes largely due to the mutational pattern.[10] Most notably, mutations and copy number alterations in PBRM1 are highly prevalent in clear cell renal cell carcinoma (ccRCC).[11]
Loss of function mutations in PBRM1 often co-occur with loss of function mutations in the VHL gene in clear cell renal cell carcinoma (ccRCC).[12] The inactivation of PBRM1 in combination with biallelic loss of VHL has been shown to potentiate HIF1α signaling and activate the pro-tumorigenic NF-κB pathway.[13][14] Genetic loss of PBRM1 is thought to underlie the early initiation of ccRCC due to the sufficiency of conditional deletion of Pbrm1 and Vhl for renal carcinomagenesis in mice.[15] While several studies have identified a favorable outcomes among advanced ccRCC cases with PBRM1 mutations when treated with immune checkpoint inhibitors, there is still debate about the utility of PBRM1 status as a biomarker for response to ICI therapy.[16][17]