Roles of the BAP1 Tumor Suppressor in Cell Metabolism

Han, Anna; Purwin, Timothy J.; Aplin, Andrew E.

doi:10.1158/0008-5472.can-20-3430

Cited by 30 publications

(34 citation statements)

References 89 publications

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“…Recent studies have demonstrated that BAP1 is also involved in several aspects of cellular metabolism, including ferroptosis [26], a recently identified form of regulated cell death that is induced by metabolic stress from cystine reduction and increased reactive oxygen species [27][28][29]. Epidemiological evidence suggests that high dietary iron intake increases the risk of several cancer types including HCC [30], and ferroptosis has been implicated in the development and therapeutic responses of various types of tumors [31].…”

Section: Discussionmentioning

confidence: 99%

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Yan¹,

Meng²,

Ding³

et al. 2022

J. Cancer

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BRCA1-Associated Protein 1 (BAP1) is a deubiquitylase that is found associated with multiprotein complexes that regulate key cellular pathways, and subsequent researches have revealed that BAP1 acts independently as a tumor suppressor. Somatic BAP1 mutations occur in various malignancies, but malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. Whether somatic mutation or expression alteration of BAP1 in hepatocellular carcinoma (HCC) influence carcinogenesis or immunogenicity is still unknown. In this study, we analyzed RNA expression, immune infiltration, survival and mutation data of HCC from The Cancer Genome Atlas databases. The association between BAP1 and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high BAP1 expression was significantly worse than that of patients with low BAP1 expression, and multivariate analyses revealed that BAP1 expression was an independent prognostic factor for poor prognosis. HCC with high BAP1 expression was associated with low ESTIMATE Score, recruitment of more tumor-infiltrating macrophage, and elevated levels of tumor mutation burden, microsatellite instability, neoantigen count, as well as programmed death-ligand1 in HCC. In addition, BAP1 mutated HCC showed reduced ability to promote ferroptosis and high BAP1 expression was correlated with ferroptosis. In conclusion, high BAP1 expression reflects immunosuppression and ferroptosis in HCC. BAP1 is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive ferroptosis-promoting therapy or immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Yan¹,

Meng²,

Ding³

et al. 2022

J. Cancer

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“…Han et al. ( 16 ) summarised and divided the metabolic roles of BAP1 into four main categories: i) nutrient homeostasis, ii) glycolytic alterations, iii) calcium dysregulation, and iv) metabolic stress management ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

“…BAP1 deficiency leads to accumulation of DNA damage, which increases the chance of neoplastic proliferation in patients with both sporadic and inherited deficiencies of BAP1. BAP1 mutations favour the development of different tumour phenotypes and have been identified in a wide range of solid tumour types, including malignant mesothelioma (MM) ( 16 , 17 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Mesothelioma and BAP1 tumor predisposition syndrome: Implications for public health

et al. 2022

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BRCA-1 associated protein 1 (BAP1) tumour predisposition syndrome (TPDS) is a hereditary condition characterised by germline mutation of the tumour suppressor BAP1. This disorder is associated with the development of various benign and malignant tumours, mainly involving the skin, eyes, kidneys, and mesothelium. In this article, we report the case of a man recruited through the Apulia (Southern Italy) Mesothelioma Regional Operational Centre of the National Register of Mesotheliomas, who suffered from uveal melanoma, renal cancer, and mesothelioma, and a familial cluster of BAP1 germline mutations demonstrated by molecular analyses. The family members of the proband developed multiple malignancies. As tumours arising in this context have specific peculiarities in terms of clinical behaviour, identification of this condition through appropriate genetic counselling should be considered for adequate primary, secondary, and tertiary prevention measures for offspring.

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“…However, when ubiquitination occurs on JosD1, it tends to localize on the cell membrane (Figure 2B) and plays a vital role in membrane dynamics, cell motility, and endocytosis (Seki et al, 2013;Zeng et al, 2020). Furthermore, BAP1, a member of the UCHs subfamily, is predominantly located in the nucleus and functions as a tumour suppressor (Cheung and Testa, 2017;Lee et al, 2020;Han et al, 2021). The lysine residues near the nuclear localization sequence (NLS) of BAP1 can be ubiquitinated, which leads to the accumulation of ubiquitinated BAP1 in the cytosol.…”

Section: Ubiquitylation Induces Changes In the Localization And Interactome Of Dubsmentioning

confidence: 99%

“…Furthermore, BAP1, a member of the UCHs subfamily, is predominantly located in the nucleus and functions as a tumour suppressor ( Cheung and Testa, 2017 ; Lee et al, 2020 ; Han et al, 2021 ). The lysine residues near the nuclear localization sequence (NLS) of BAP1 can be ubiquitinated, which leads to the accumulation of ubiquitinated BAP1 in the cytosol.…”

Section: Ptms Can Regulate the Localization Of Dubsmentioning

confidence: 99%

Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code

Wang

2021

Front. Pharmacol.

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Post-translational modifications such as ubiquitination play important regulatory roles in several biological processes in eukaryotes. This process could be reversed by deubiquitinating enzymes (DUBs), which remove conjugated ubiquitin molecules from target substrates. Owing to their role as essential enzymes in regulating all ubiquitin-related processes, the abundance, localization, and catalytic activity of DUBs are tightly regulated. Dysregulation of DUBs can cause dramatic physiological consequences and a variety of disorders such as cancer, and neurodegenerative and inflammatory diseases. Multiple factors, such as transcription and translation of associated genes, and the presence of accessory domains, binding proteins, and inhibitors have been implicated in several aspects of DUB regulation. Beyond this level of regulation, emerging studies show that the function of DUBs can be regulated by a variety of post-translational modifications, which significantly affect the abundance, localization, and catalytic activity of DUBs. The most extensively studied post-translational modification of DUBs is phosphorylation. Besides phosphorylation, ubiquitination, SUMOylation, acetylation, oxidation, and hydroxylation are also reported in DUBs. In this review, we summarize the current knowledge on the regulatory effects of post-translational modifications of DUBs.

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Roles of the BAP1 Tumor Suppressor in Cell Metabolism

Cited by 30 publications

References 89 publications

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Somatic mutation and expression of BAP1 in hepatocellular carcinoma: an indicator for ferroptosis and immune checkpoint inhibitor therapies

Case report: Mesothelioma and BAP1 tumor predisposition syndrome: Implications for public health

Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code

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