IndraLab

"The loss of the ring finger domain abrogates the binding of BARD1 and BAP1, which are important regulators of E3 ubiquitin ligase activity of BRCA1."

"BAP1 binding to BARD1 results in inhibition of the E3 ligase activity of BRCA1/BARD1 via the prevention of RING heterodimer formation ( xref et al. , 2009)."

"BAP1, a ubiquitin carboxy-terminal hydrolase, interacts with the RING finger domain of BARD1 to inhibit the E3 ligase activity of BRCA1/BARD1, protecting BRCA1 from proteasome-mediated degradation ( xref , xref )."

"BAP1 binds and deubiquitylates BARD1, thus modulating the E3 ligase activity of BRCA1-BARD1 28."

"BAP1 binds and deubiquitylates BARD1, thus modulating the E3 ligase activity of BRCA1–BARD1 xref ."

"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1 and BARD1 complex, and that BAP1 and BRCA1 and BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway."

"BAP1 binds to the BRCA1-associated RING domain protein 1 (BARD1) and inhibits E3 ubiquitin ligase activity of the BRCA1/BARD1 complex, which modulates the DNA damage response ( xref )."

"BAP1 also directly interacts with BARD1."

"Several studies later demonstrated that BAP1 mainly interacts with BARD1 perturbing BARD1/BRCA1 complex [ xref ]."

"Domains comprised by residues 182-365 of BAP1 interact with the RING finger domain of BARD1, and surface plasmon resonance spectroscopy (BIAcore) analyses showed that BAP1 interferes with the BRCA1/BARD1 association."

"UCH is involved in the de-ubiquitin activity of BAP1 [ xref ], and BAP1 interacts with BARD1 to inhibit the E3 ligase activity of BRCA1-BARD1 complex."

"Until recently, the combination of pemetrexed and cisplatin was the only approved first-line therapy, yielding a median overall survival (OS) of 12.1 months.2 Nivolumab plus ipilimumab was approved recently as initial treatment for malignant pleural mesothelioma (MPM) on the basis of a phase 3 clinical trial that resulted in a median OS of 18.1 months.3 4 There are no approved therapies for patients with tumor relapse after first-line therapies.Risk factors in developing mesothelioma include exposure to asbestos5 and other carcinogenic fibers such as erionite,6 and previous radiation therapy.7 8 Studies of familial clusters of mesothelioma have revealed genetic predisposition to develop MM.9 10 Recent work has identified germline mutations in BAP1 that can predispose to mesothelioma11 12 and other cancers such as uveal and cutaneous melanoma, basal cell carcinoma, meningioma, and renal cell cancers.13 14 We previously identified deleterious germline mutations in 12% of 241 consecutive patients with MM who enrolled on a prospective natural history study, with BAP1 being the most frequent germline mutation.15 BAP1 was also recurrently inactivated at the somatic level, suggesting BAP1 variants undergoing positive selection in the context of the classic “two-hit” model.BAP1, a nuclear deubiquitylase, was initially discovered as an interaction partner of the tumor suppressor BRCA1.16 Subsequent studies revealed that BAP1 binds to BARD1, which, in turn, binds to BRCA1, forming the BRCA1-BARD1-BAP1 complex that is crucial for the homologous recombination (HR)–mediated repair of DNA double-strand breaks (DSBs).17 PARP enzymes play a major role in DNA single-strand break repair and base excision repair pathways."

"Here, we report that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of BRCA1 and BARD1."

"Here, we report that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of BRCA1/BARD1."

"BAP1 interacts with BARD1 (182aeuro " 365), HCF-1 (365aeuro " 385), BRCA1 (596aeuro " 721) and YY1 (642- 686).10,88 Numbers refer to amino acid positions."

"BAP1 binds to BARD1 to form a BRCA1–BARD1–BAP1 complex that is involved in the homologous recombination (HR)-mediated repair of double-strand DNA breaks (BSBs)."

"This RING-finger domain is a zinc-binding motif which can bind BARD1 and BAP1 [ xref , xref ]."

"The involvement of BAP1 in HR may be regulated by the BAP1–BARD1 binding ( xref )."

"Since BARD1 directly interacts with BAP1, the major impact of mutations in BARD1 (E182G, G185R) as compared to BRCA1 (E602D) can be seen in the structural analysis."

"Briefly, BAP1 interacts with BRCA1/ BARD1 complex to regulate crucial biological processes, such as chromatin modification, DNA damage repair and cell cycle control xref , xref ."

"The loss of the ring finger domain abrogates the binding of BARD1 and BAP1, which are important regulators of E3 ubiquitin ligase activity of BRCA1."

"We reasoned that if BAP1 interacts with BARD1 to modulate homologous recombination and possibly other cellular pathways, germline BARD1 mutations might also predispose to mesothelioma, and that these patients might have a better prognosis, similar to carriers of germline BAP1 mutations."

"The E3 ligase activity of the BRCA1-BARD1 tumor-suppressor complex is suppressed by the interaction of BAP1 with BARD1 through its deubiquitylation."

"The RING finger domain has been shown to mediate interactions with both BARD1 (see below) and a ubiquitin C-terminal hydrolase BAP1 [18] ."

"At the amino terminus is a zinc-binding RINGfinger domain, containing a cys3-his-cys4 structure, which binds BARD1 (BRCA1-associated RING domain protein) and BAP1 (BRCA1-associated protein) – hallmarks of the RING-finger family of transcriptional regulatory proteins."