BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability

Lee, Shin-Ai; Lee, Daye; Kang, Minhwa; Kwon, Su-Jung; Lee, Han-Sae; Seo, Hye-Ran; Kaushal, Prashant; Lee, Nam Soo; Kim, Hongtae; Lee, Cheolju; Kwon, Jongbum

doi:10.1038/s41418-022-01024-w

Cited by 18 publications

(23 citation statements)

References 64 publications

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“…The DUB activity of BAP1 was measured using the ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) DUB assay system (Boston Biochem) as previously described 19 . In brief, Ub-AMC was incubated with His-Flag-BAP1 or His-Flag-BAP1-C91S in a black 96-well plate at RT, and fluorescence signals were measured every 15 s using a SpectraMax i3X microplate reader (I3X-SC-ACAD, Molecular Devices) at an excitation wavelength of 350 nm and an emission wavelength of 455 nm.…”

Section: Dub Activity Assay With Ub-amcmentioning

confidence: 99%

“…www.nature.com/scientificreports/ DUB assay with H2A-Ub mononucleosomes. The DUB assay using H2A-Ub nucleosome substrates was performed as previously described 19 . In brief, TG2-179-1 was mixed with His-Flag-BAP1 or His-Flag-BAP1-C91S, and the reactions were incubated with H2A-Ub mononucleosomes (EpiCypher) and ASXL1 DEU in DUB buffer (50 mM Tris-Cl (pH 7.5), 50 mM NaCl 2 , 1 mM MgCl 2 , and 1 mM DTT) at RT for 90 min.…”

Section: Dub Activity Assay With Ub-amcmentioning

confidence: 99%

“…Preparation of recombinant proteins. His-Flag-BAP1, His-Flag-BAP1-C91S and His-ASXL1 DEU were expressed in and purified from E. coli as previously described 19 .…”

Section: Dub Activity Assay With Ub-amcmentioning

confidence: 99%

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Targeting BAP1 with small compound inhibitor for colon cancer treatment

Kang

Park

Lee

et al. 2023

Sci Rep

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BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase. The gene encoding BAP1 is mutated in various human cancers, including mesothelioma, uveal melanoma and renal cell carcinoma. BAP1 plays roles in many cancer-related cellular functions, including cell proliferation, cell death, and nuclear processes crucial for genome stability, such as DNA repair and replication. While these findings suggest that BAP1 functions as a tumor suppressor, recent data also suggest that BAP1 might play tumor-promoting roles in certain cancers, such as breast cancer and hematopoietic malignancies. Here, we show that BAP1 is upregulated in colon cancer cells and tissues and that BAP1 depletion reduces colon cancer cell proliferation and tumor growth. BAP1 contributes to colon cancer cell proliferation by accelerating DNA replication and suppressing replication stress and concomitant apoptosis. A recently identified BAP1 inhibitor, TG2-179-1, which seems to covalently bind to the active site of BAP1, exhibits potent cytotoxic activity against colon cancer cells, with half-maximal inhibitory concentrations of less than 10 μM, and inhibits colon tumor growth. TG2-179-1 exerts cytotoxic activity by targeting BAP1, leading to defective replication and increased apoptosis. This work therefore shows that BAP1 acts oncogenically in colon cancer and is a potential therapeutic target for this cancer. Our work also suggests that TG2-179-1 can be developed as a potential therapeutic agent for colon cancer.

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Section: Dub Activity Assay With Ub-amcmentioning

confidence: 99%

Section: Dub Activity Assay With Ub-amcmentioning

confidence: 99%

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Targeting BAP1 with small compound inhibitor for colon cancer treatment

Kang

Park

Lee

et al. 2023

Sci Rep

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“…BAP1 functions as a tumor suppressor and deubiquitinating enzyme, regulating the cellular processes of DNA repair, genomic stability and cell cycle regulation following Knudson’s two hit hypothesis, in a manner similar to VHL [ 161 , 162 , 163 , 164 ]. Additionally, similar to VHL, BAP1 functions as a protein complex [ 165 , 166 ].…”

Section: Brca-associated Protein 1 Tumor Predisposition Syndrome (Bap1)mentioning

confidence: 99%

Tumorigenesis Mechanisms Found in Hereditary Renal Cell Carcinoma: A Review

Webster

Gopal

Ball

2022

Genes

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Renal cell carcinoma is a heterogenous cancer composed of an increasing number of unique subtypes each with their own cellular and tumor behavior. The study of hereditary renal cell carcinoma, which composes just 5% of all types of tumor cases, has allowed for the elucidation of subtype-specific tumorigenesis mechanisms that can also be applied to their sporadic counterparts. This review will focus on the major forms of hereditary renal cell carcinoma and the genetic alterations contributing to their tumorigenesis, including von Hippel Lindau syndrome, Hereditary Papillary Renal Cell Carcinoma, Succinate Dehydrogenase-Deficient Renal Cell Carcinoma, Hereditary Leiomyomatosis and Renal Cell Carcinoma, BRCA Associated Protein 1 Tumor Predisposition Syndrome, Tuberous Sclerosis, Birt–Hogg–Dubé Syndrome and Translocation RCC. The mechanisms for tumorigenesis described in this review are beginning to be exploited via the utilization of novel targets to treat renal cell carcinoma in a subtype-specific fashion.

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“…BAP1 and PR-DUB remove ubiquitin from H2A-K119-ub and H2A-K118-ub (both denoted H2Aub hereafter), respectively, which are the transcriptional histone markers catalyzed by the Polycomb (PcG) group complex PRC1 32,33 . BAP1 participates in a wide range of biological processes by directly targeting proteins as substrates or indirectly via transcription, and these BAP1regulated processes include cell cycle control [28][29][30]34,35 , cell survival and proliferation 32,36,37 , cell death [38][39][40][41][42][43] , the DNA damage response (DDR) and repair [44][45][46][47] , DNA replication [48][49][50][51] , metabolism 39,[52][53][54] , and cell differentiation and development 36,[55][56][57] . For example, BAP1 promotes apoptosis by deubiquitinating and stabilizing IP3R3 at the endoplasmic reticulum (ER), which stimulates Ca 2+ release from the ER into the cytosol and thereby increases the mitochondrial Ca 2+ concentration and cytochrome C release 41 .…”

Section: Introductionmentioning

confidence: 99%

BAP1 as a guardian of genome stability: implications in human cancer

Kwon

Lee

2023

Exp Mol Med

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BAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the BAP1 gene have been identified in multiple human cancers, with a particularly high frequency in mesothelioma, uveal melanoma and clear cell renal cell carcinoma. BAP1 cancer syndrome highlights that all carriers of inherited BAP1-inactivating mutations develop at least one and often multiple cancers with high penetrance during their lifetime. These findings, together with substantial evidence indicating the involvement of BAP1 in many cancer-related biological activities, strongly suggest that BAP1 functions as a tumor suppressor. Nonetheless, the mechanisms that account for the tumor suppressor function of BAP1 have only begun to be elucidated. Recently, the roles of BAP1 in genome stability and apoptosis have drawn considerable attention, and they are compelling candidates for key mechanistic factors. In this review, we focus on genome stability and summarize the details of the cellular and molecular functions of BAP1 in DNA repair and replication, which are crucial for genome integrity, and discuss the implications for BAP1-associated cancer and relevant therapeutic strategies. We also highlight some unresolved issues and potential future research directions.

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BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability

Cited by 18 publications

References 64 publications

Targeting BAP1 with small compound inhibitor for colon cancer treatment

Targeting BAP1 with small compound inhibitor for colon cancer treatment

Tumorigenesis Mechanisms Found in Hereditary Renal Cell Carcinoma: A Review

BAP1 as a guardian of genome stability: implications in human cancer

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