PBRM1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPBRM1, BAF180, PB1, polybromo 1, SMARCH1, RCC
External IDsOMIM: 606083 MGI: 1923998 HomoloGene: 10044 GeneCards: PBRM1
Orthologs
SpeciesHumanMouse
Entrez

55193

66923

Ensembl

ENSG00000163939

ENSMUSG00000042323

UniProt

Q86U86

Q8BSQ9

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 3: 52.55 – 52.69 MbChr 14: 30.74 – 30.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Structure and function

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]

Clinical significance

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]

Role renal carcinoma

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]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000163939 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042323 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Xue Y, Canman JC, Lee CS, Nie Z, Yang D, Moreno GT, et al. (November 2000). "The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes". Proceedings of the National Academy of Sciences of the United States of America. 97 (24): 13015–13020. Bibcode:2000PNAS...9713015X. doi:10.1073/pnas.240208597. PMC 27170. PMID 11078522.
  6. ↑ Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, et al. (August 2001). "Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs". Genome Research. 11 (8): 1392–1403. doi:10.1101/gr.175501. PMC 311073. PMID 11483580.
  7. ↑ "Entrez Gene: PB1 polybromo 1".
  8. ↑ Mashtalir N, D'Avino AR, Michel BC, Luo J, Pan J, Otto JE, et al. (November 2018). "Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes". Cell. 175 (5): 1272–1288.e20. doi:10.1016/j.cell.2018.09.032. PMC 6791824. PMID 30343899.
  9. ↑ "Q86U86 : Protein polybromo-1 (Human)". Universal Protein Resource. UniProt Consortium.
  10. ↑ Shain AH, Pollack JR (2013). "The spectrum of SWI/SNF mutations, ubiquitous in human cancers". PLOS ONE. 8 (1): e55119. Bibcode:2013PLoSO...855119S. doi:10.1371/journal.pone.0055119. PMC 3552954. PMID 23355908.
  11. ↑ Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, et al. (January 2011). "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma". Nature. 469 (7331): 539–542. Bibcode:2011Natur.469..539V. doi:10.1038/nature09639. PMC 3030920. PMID 21248752.
  12. ↑ Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, et al. (January 2011). "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma". Nature. 469 (7331): 539–542. Bibcode:2011Natur.469..539V. doi:10.1038/nature09639. PMC 3030920. PMID 21248752.
  13. ↑ Gao W, Li W, Xiao T, Liu XS, Kaelin WG (January 2017). "Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma". Proceedings of the National Academy of Sciences of the United States of America. 114 (5): 1027–1032. Bibcode:2017PNAS..114.1027G. doi:10.1073/pnas.1619726114. PMC 5293026. PMID 28082722.
  14. ↑ Yao X, Hong JH, Nargund AM, Ng MS, Heng HL, Li Z, et al. (May 2023). "PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma". Nature Cell Biology. 25 (5): 765–777. doi:10.1038/s41556-023-01122-y. PMID 37095322. S2CID 258311941.
  15. ↑ Gu YF, Cohn S, Christie A, McKenzie T, Wolff N, Do QN, et al. (August 2017). "Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade". Cancer Discovery. 7 (8): 900–917. doi:10.1158/2159-8290.CD-17-0292. PMC 5540776. PMID 28473526.
  16. ↑ Yang Q, Shen R, Xu H, Shi X, Xu L, Zhang L, et al. (March 2021). "Comprehensive analyses of PBRM1 in multiple cancer types and its association with clinical response to immunotherapy and immune infiltrates". Annals of Translational Medicine. 9 (6): 465. doi:10.21037/atm-21-289. PMC 8039713. PMID 33850862.
  17. ↑ Carril-Ajuria L, Santos M, Roldán-Romero JM, Rodriguez-Antona C, de Velasco G (December 2019). "Prognostic and Predictive Value of PBRM1 in Clear Cell Renal Cell Carcinoma". Cancers. 12 (1): 16. doi:10.3390/cancers12010016. PMC 7016957. PMID 31861590.

Further reading


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