BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression.
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.
Jensen
D E
DE
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Proctor
M
M
Marquis
S T
ST
Gardner
H P
HP
Ha
S I
SI
Chodosh
L A
LA
Ishov
A M
AM
Tommerup
N
N
Vissing
H
H
Sekido
Y
Y
Minna
J
J
Borodovsky
A
A
Schultz
D C
DC
Wilkinson
K D
KD
Maul
G G
GG
Barlev
N
N
Berger
S L
SL
Prendergast
G C
GC
Rauscher
F J
FJ
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
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