a ubiquitin carboxyl-terminal hydrolase (UCH)
N-terminus catalytic domain, which removes
ubiquitin from ubiquitylated substrates: residues 1-240, with an active site comprising the
Cysteine91,
Alanine95, and
Glycine178 residues.
In both Drosophila and humans, BAP1 functions as the catalytic subunit of the Polycomb repressive deubiquitinase (PR-DUB) complex, which controls
homeobox genes by regulating the amount of ubiquitinated
Histone H2A in
Nucleosomes bound to their
promoters. In flies and humans, the PR-DUB complex is formed through the interaction of BAP1 and
ASXL1 (
Asx in
fruit flies)[8][9] BAP1 has also been shown to associate with other factors involved in chromatin modulation and transcriptional regulation, such as
Host cell factor C1,[10][11][12] which acts as an adaptor to couple
E2F transcription factors to
chromatin-modifying complexes during
cell cycle progression.
BAP1 mutations have been identified in aggressive
mesotheliomas with similar mutations as seen in melanomas,.[15]
Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma (CCRCC) cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma.[16]
Immunohistochemistry for BAP1 is a prognostic biomarker to predict poor oncologic outcomes and adverse clinicopathological features in patients with non-metastatic
clear cell renal cell carcinoma (CCRCC). BAP1 assessment using immunohistochemistry on
needle biopsy may benefit preoperative risk stratification and guide treatment planning.[21]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^
abcdJensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM, Tommerup N, Vissing H, Sekido Y, Minna J, Borodovsky A, Schultz DC, Wilkinson KD, Maul GG, Barlev N, Berger SL, Prendergast GC, Rauscher FJ (Mar 1998). "BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression". Oncogene. 16 (9): 1097–112.
doi:
10.1038/sj.onc.1201861.
PMID9528852.
S2CID1019611.
^Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, Windpassinger C, Wackernagel W, Loy S, Wolf I, Viale A, Lash AE, Pirun M, Socci ND, Rütten A, Palmedo G, Abramson D, Offit K, Ott A, Becker JC, Cerroni L, Kutzner H, Bastian BC, Speicher MR (Oct 2011).
"Germline mutations in BAP1 predispose to melanocytic tumors". Nature Genetics. 43 (10): 1018–21.
doi:
10.1038/ng.910.
PMC3328403.
PMID21874003.
^Heydrich CE, Schneider KA, Rana Q (2015). "When to Consider Referral to a Genetic Counselor for Lesser Known Cancer Syndromes". Contemporary Oncology. 7 (1): 26–32.
Zhou ZR, Zhang YH, Liu S, Song AX, Hu HY (Jan 2012). "Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains". The Biochemical Journal. 441 (1): 143–9.
doi:
10.1042/BJ20110699.
PMID21851340.
Jensen DE, Rauscher FJ (Sep 1999). "Defining biochemical functions for the BRCA1 tumor suppressor protein: analysis of the BRCA1 binding protein BAP1". Cancer Letters. 143 (Suppl 1): S13-7.
doi:
10.1016/s0304-3835(99)90004-6.
PMID10546591.
a ubiquitin carboxyl-terminal hydrolase (UCH)
N-terminus catalytic domain, which removes
ubiquitin from ubiquitylated substrates: residues 1-240, with an active site comprising the
Cysteine91,
Alanine95, and
Glycine178 residues.
In both Drosophila and humans, BAP1 functions as the catalytic subunit of the Polycomb repressive deubiquitinase (PR-DUB) complex, which controls
homeobox genes by regulating the amount of ubiquitinated
Histone H2A in
Nucleosomes bound to their
promoters. In flies and humans, the PR-DUB complex is formed through the interaction of BAP1 and
ASXL1 (
Asx in
fruit flies)[8][9] BAP1 has also been shown to associate with other factors involved in chromatin modulation and transcriptional regulation, such as
Host cell factor C1,[10][11][12] which acts as an adaptor to couple
E2F transcription factors to
chromatin-modifying complexes during
cell cycle progression.
BAP1 mutations have been identified in aggressive
mesotheliomas with similar mutations as seen in melanomas,.[15]
Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma (CCRCC) cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma.[16]
Immunohistochemistry for BAP1 is a prognostic biomarker to predict poor oncologic outcomes and adverse clinicopathological features in patients with non-metastatic
clear cell renal cell carcinoma (CCRCC). BAP1 assessment using immunohistochemistry on
needle biopsy may benefit preoperative risk stratification and guide treatment planning.[21]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^
abcdJensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM, Tommerup N, Vissing H, Sekido Y, Minna J, Borodovsky A, Schultz DC, Wilkinson KD, Maul GG, Barlev N, Berger SL, Prendergast GC, Rauscher FJ (Mar 1998). "BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression". Oncogene. 16 (9): 1097–112.
doi:
10.1038/sj.onc.1201861.
PMID9528852.
S2CID1019611.
^Wiesner T, Obenauf AC, Murali R, Fried I, Griewank KG, Ulz P, Windpassinger C, Wackernagel W, Loy S, Wolf I, Viale A, Lash AE, Pirun M, Socci ND, Rütten A, Palmedo G, Abramson D, Offit K, Ott A, Becker JC, Cerroni L, Kutzner H, Bastian BC, Speicher MR (Oct 2011).
"Germline mutations in BAP1 predispose to melanocytic tumors". Nature Genetics. 43 (10): 1018–21.
doi:
10.1038/ng.910.
PMC3328403.
PMID21874003.
^Heydrich CE, Schneider KA, Rana Q (2015). "When to Consider Referral to a Genetic Counselor for Lesser Known Cancer Syndromes". Contemporary Oncology. 7 (1): 26–32.
Zhou ZR, Zhang YH, Liu S, Song AX, Hu HY (Jan 2012). "Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains". The Biochemical Journal. 441 (1): 143–9.
doi:
10.1042/BJ20110699.
PMID21851340.
Jensen DE, Rauscher FJ (Sep 1999). "Defining biochemical functions for the BRCA1 tumor suppressor protein: analysis of the BRCA1 binding protein BAP1". Cancer Letters. 143 (Suppl 1): S13-7.
doi:
10.1016/s0304-3835(99)90004-6.
PMID10546591.