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BAP1 disrupts the BRCA1:BARD1 heterodimer
Stable Identifier
R-HSA-9700998
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
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DNA Repair (Homo sapiens)
DNA Double-Strand Break Repair (Homo sapiens)
DNA Double Strand Break Response (Homo sapiens)
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (Homo sapiens)
BAP1 disrupts the BRCA1:BARD1 heterodimer (Homo sapiens)
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Binding of BAP1 to the BRCA1:BARD1 heterodimer disrupts the BRCA1:BARD1 association and consequently inhibits its E3 ubiquitin ligase activity. Downregulation of BAP1 expression results in the hypersensitivity of cells to ionizing radiation and in retardation of S phase progression, suggesting that BAP1 coordinates the enzymatic activity of the BRCA1:BARD1 complex during DNA double strand break response and during cell cycle (Nishikawa et al. 2009). While BAP1 is a deubiquitinating enzyme and may deubiquitinate some BRCA1:BARD1 substrates, it does not deubiquitinate autoubiquitinated BRCA1 and BARD1 (Mallery et al. 2002, Nishikawa et al. 2009). A catalytically-inactive mutant of BAP1, BAP1 C91S, is still able to inhibit BRCA1:BARD1-mediated ubiquitination, implying that BAP1 primarily regulates the action of the BRCA1:BARD1 complex by disrupting it (Nishikawa et al. 2009).
Literature References
PubMed ID
Title
Journal
Year
19117993
BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity
Kojima, R
,
Fukuda, M
,
Koike, A
,
Nishikawa, H
,
Ohta, T
,
Wu, W
,
Gomi, H
Cancer Res.
2009
Participants
Input
BRCA1:BARD1:BAP1 [nucleoplasm]
(Homo sapiens)
Output
BAP1:BARD1 [nucleoplasm]
(Homo sapiens)
BRCA1 [nucleoplasm]
(Homo sapiens)
Participates
as an event of
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (Homo sapiens)
Orthologous Events
BAP1 disrupts the BRCA1:BARD1 heterodimer (Bos taurus)
BAP1 disrupts the BRCA1:BARD1 heterodimer (Canis familiaris)
BAP1 disrupts the BRCA1:BARD1 heterodimer (Gallus gallus)
BAP1 disrupts the BRCA1:BARD1 heterodimer (Mus musculus)
BAP1 disrupts the BRCA1:BARD1 heterodimer (Rattus norvegicus)
BAP1 disrupts the BRCA1:BARD1 heterodimer (Sus scrofa)
Authored
Orlic-Milacic, M (2020-09-30)
Reviewed
Baer, RJ (2020-11-04)
Created
Orlic-Milacic, M (2020-09-23)
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