title: BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression.
abstract: We have identified a novel protein, BAP1, which binds to the RING finger domain of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1. BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function. BAP1 binds to the wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger found in breast cancer kindreds. BAP1 and BRCA1 are temporally and spatially co-expressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3; intragenic homozygous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines. BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal hydrolase to be identified. BAP1 may be a new tumor suppressor gene which functions in the BRCA1 growth control pathway.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Proctor
authors.forename: S T
authors.initials: ST
authors.lastname: Marquis
authors.forename: H P
authors.initials: HP
authors.lastname: Gardner
authors.forename: S I
authors.initials: SI
authors.lastname: Ha
authors.forename: L A
authors.initials: LA
authors.lastname: Chodosh
authors.forename: A M
authors.initials: AM
authors.lastname: Ishov
authors.forename: N
authors.initials: N
authors.lastname: Tommerup
authors.forename: H
authors.initials: H
authors.lastname: Vissing
authors.forename: Y
authors.initials: Y
authors.lastname: Sekido
authors.forename: J
authors.initials: J
authors.lastname: Minna
authors.forename: A
authors.initials: A
authors.lastname: Borodovsky
authors.forename: D C
authors.initials: DC
authors.lastname: Schultz
authors.forename: K D
authors.initials: KD
authors.lastname: Wilkinson
authors.forename: G G
authors.initials: GG
authors.lastname: Maul
authors.forename: N
authors.initials: N
authors.lastname: Barlev
authors.forename: S L
authors.initials: SL
authors.lastname: Berger
authors.forename: G C
authors.initials: GC
authors.lastname: Prendergast
authors.forename: F J
authors.initials: FJ
authors.lastname: Rauscher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005260:Female; D015321:Gene Rearrangement; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D008175:Lung Neoplasms / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
chemical_list: C575444:BAP1 protein, mouse; D019313:BRCA1 Protein; D002352:Carrier Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; C491163:Bard1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase