[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Progress
  • Published:

BAP1 and cancer

Nature Reviews Cancer volume 13, pages 153–159 (2013)Cite this article

Subjects

Abstract

BAP1 is a deubiquitylase that is found associated with multiprotein complexes that regulate key cellular pathways, including the cell cycle, cellular differentiation, cell death, gluconeogenesis and the DNA damage response (DDR). Recent findings indicate that germline BAP1 mutations cause a novel cancer syndrome that is characterized, at least in the affected families that have been studied so far, by the onset at an early age of benign melanocytic skin tumours with mutated BAP1, and later in life by a high incidence of mesothelioma, uveal melanoma, cutaneous melanoma and possibly additional cancers.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: BAP1 protein partners and proposed functions.
Figure 2: Schematic representation of BAP1 domains and locations of the reported BAP1 germline mutations.

Similar content being viewed by others

References

  1. Carbone, M. et al. A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes. Nature Rev. Cancer 7, 147–154 (2007).

    Article  CAS  Google Scholar 

  2. Carbone, M. & Yang, H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin. Cancer Res. 18, 598–604 (2012).

    Article  CAS  Google Scholar 

  3. Carbone, M. et al. Erionite exposure in North Dakota and Turkish villages with mesothelioma. Proc. Natl Acad. Sci. USA 108, 13618–13623 (2011).

    Article  CAS  Google Scholar 

  4. Roushdy-Hammady, I., Siegel, J., Emri, S., Testa, J. R. & Carbone, M. Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey. Lancet 357, 444–445 (2001).

    Article  CAS  Google Scholar 

  5. Dogan, A. U. et al. Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey. Cancer Res. 66, 5063–5068 (2006).

    Article  CAS  Google Scholar 

  6. Testa, J. R. et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nature Genet. 43, 1022–1025 (2011).

    Article  CAS  Google Scholar 

  7. Harbour, J. W. et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330, 1410–1413 (2010).

    Article  CAS  Google Scholar 

  8. Lu, Y. Y., Jhanwar, S. C., Cheng, J. Q. & Testa, J. R. Deletion mapping of the short arm of chromosome 3 in human malignant mesothelioma. Genes Chromosomes Cancer 9, 76–80 (1994).

    Article  CAS  Google Scholar 

  9. Zeiger, M. A., Gnarra, J. R., Zbar, B., Linehan, W. M. & Pass, H. I. Loss of heterozygosity on the short arm of chromosome 3 in mesothelioma cell lines and solid tumors. Genes Chromosomes Cancer 11, 15–20 (1994).

    Article  CAS  Google Scholar 

  10. Wiesner, T. et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nature Genet. 43, 1018–1021 (2011).

    Article  CAS  Google Scholar 

  11. Wiesner, T. et al. A distinct subset of atypical spitz tumors is characterized by BRAF mutation and loss of BAP1 expression. Am. J. Surg. Pathol. 36, 818–830 (2012).

    Article  Google Scholar 

  12. Carbone, M. et al. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J. Transl. Med. 1066, 179 (2012).

    Article  Google Scholar 

  13. Njauw, C. N. et al. Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families. PLoS ONE 766, e35295 (2012).

    Article  Google Scholar 

  14. Wiesner, T. et al. Toward an improved definition of the tumor spectrum associated with BAP1 germline mutations. J. Clin. Oncol. 30, e337–e340 (2012).

    Article  Google Scholar 

  15. Cagianut, B. Melanoma of the choroid and ciliary body, malignant meningioma and mesothelioma of the pleura (triple-malignoma) in a 63-year old female. Klin. Monbl. Augenheilkd. 161, 407–411 (1972).

    CAS  PubMed  Google Scholar 

  16. Abdel-Rahman, M. H. et al. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J. Med. Genet. 48, 856–859 (2011).

    Article  CAS  Google Scholar 

  17. Aoude, L. G., Vajdic, C. M., Kricker, A., Armstrong, B. & Hayward, N. K. Prevalence of germline BAP1 mutation in a population-based sample of uveal melanoma cases. Pigment Cell Melanoma Res. 11 Dec 2012 (doi:10.1111/pcmr.12046).

  18. Pena-Llopis, S. et al. BAP1 loss defines a new class of renal cell carcinoma. Nature Genet. 44, 751–759 (2012).

    Article  CAS  Google Scholar 

  19. Wadt, K. et al. A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma. Pigment Cell Melanoma Res. 25, 815–818 (2012).

    Article  CAS  Google Scholar 

  20. Begg, C. B. et al. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J. Natl Cancer Inst. 97, 1507–1515 (2005).

    Article  CAS  Google Scholar 

  21. Li, F. P. & Fraumeni, J. F. Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann. Intern. Med. 71, 747–752 (1969).

    Article  CAS  Google Scholar 

  22. Bheda, A., Shackelford, J. & Pagano, J. S. Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated genes. PLoS ONE 466, e6764 (2009).

    Article  Google Scholar 

  23. Fang, Y., Fu, D. & Shen, X. Z. The potential role of ubiquitin c-terminal hydrolases in oncogenesis. Biochim. Biophys. Acta 1806, 1–6 (2010).

    CAS  PubMed  Google Scholar 

  24. Jensen, D. E. et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 16, 1097–1112 (1998).

    Article  CAS  Google Scholar 

  25. Bott, M. et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nature Genet. 43, 668–672 (2011).

    Article  CAS  Google Scholar 

  26. Mallery, D. L., Vandenberg, C. J. & Hiom, K. Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains. EMBO J. 21, 6755–6762 (2002).

    Article  CAS  Google Scholar 

  27. Greenberg, R. A. et al. Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes. Genes Dev. 20, 34–46 (2006).

    Article  CAS  Google Scholar 

  28. Nishikawa, H. et al. BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity. Cancer Res. 69, 111–119 (2009).

    Article  CAS  Google Scholar 

  29. Ventii, K. H. et al. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res. 68, 6953–6962 (2008).

    Article  CAS  Google Scholar 

  30. Machida, Y. J., Machida, Y., Vashisht, A. A., Wohlschlegel, J. A. & Dutta, A. The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J. Biol. Chem. 284, 34179–34188 (2009).

    Article  CAS  Google Scholar 

  31. Misaghi, S. et al. Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1. Mol. Cell. Biol. 29, 2181–2192 (2009).

    Article  CAS  Google Scholar 

  32. Tyagi, S., Chabes, A. L., Wysocka, J. & Herr, W. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol. Cell 27, 107–119 (2007).

    Article  CAS  Google Scholar 

  33. Eletr, Z. M. & Wilkinson, K. D. An emerging model for BAP1's role in regulating cell cycle progression. Cell Biochem. Biophys. 60, 3–11 (2011).

    Article  CAS  Google Scholar 

  34. Scheuermann, J. C. et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465, 243–247 (2010).

    Article  CAS  Google Scholar 

  35. Simon, J. A. & Kingston, R. E. Mechanisms of polycomb gene silencing: knowns and unknowns. Nature Rev. Mol. Cell Biol. 10, 697–708 (2009).

    Article  CAS  Google Scholar 

  36. Gutierrez, L. et al. The role of the histone H2A ubiquitinase Sce in Polycomb repression. Development 139, 117–127 (2012).

    Article  CAS  Google Scholar 

  37. Zhu, Q. et al. BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477, 179–184 (2011).

    Article  CAS  Google Scholar 

  38. Kemp, C. D. et al. Polycomb repressor complex-2 is a novel target for mesothelioma therapy. Clin. Cancer Res. 18, 77–90 (2012).

    Article  CAS  Google Scholar 

  39. Yu, H. et al. The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Mol. Cell. Biol. 30, 5071–5085 (2010).

    Article  CAS  Google Scholar 

  40. Gambetta, M. C., Oktaba, K. & Muller, J. Essential role of the glycosyltransferase sxc/Ogt in polycomb repression. Science 325, 93–96 (2009).

    Article  CAS  Google Scholar 

  41. Dey, A. et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 337, 1541–1546 (2012).

    Article  CAS  Google Scholar 

  42. Ruan, H. B. et al. O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by modulating PGC-1α stability. Cell Metab. 16, 226–237 (2012).

    Article  CAS  Google Scholar 

  43. Yoshikawa, Y. et al. Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 103, 868–874 (2012).

    Article  CAS  Google Scholar 

  44. Jube, S. et al. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res 72, 3290–3301 (2012).

    Article  CAS  Google Scholar 

  45. Celona, B. et al. Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS Biol. 966, e1001086 (2011).

    Article  Google Scholar 

  46. Horn, E. P., Hartge, P., Shields, J. A. & Tucker, M. A. Sunlight and risk of uveal melanoma. J. Natl Cancer Inst. 86, 1476–1478 (1994).

    Article  CAS  Google Scholar 

  47. Stokes, M. P. et al. Profiling of UV-induced ATM/ATR signaling pathways. Proc. Natl Acad. Sci. USA 104, 19855–19860 (2007).

    Article  CAS  Google Scholar 

  48. Landreville, S. et al. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin. Cancer Res. 18, 408–416 (2012).

    Article  CAS  Google Scholar 

  49. Flores, R. M. et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J. Thorac. Cardiovasc. Surg. 135, 620–626.e3 (2008).

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the W and L family members for their participation in this study, and F. Baumann, E. Flores, S. Kanodia, A. Napolitano, J. D. Rowley and D. C. Ward for critical reading of this manuscript. They thank T. Wiesner for sharing MBAIT tissue specimens for their review. NCI PO1 CA 1140047 to M.C. supported this work.

Author information

Authors and Affiliations

  1. Michele Carbone, Haining Yang and Giovanni Gaudino are at the University of Hawaii Cancer Center, BSB200, 701 Ilalo Street, Honolulu, Hawaii 96813, USA.,

    Michele Carbone, Haining Yang & Giovanni Gaudino

  2. Haining Yang and Michele Carbone are also at the Department of Pathology at the University of Hawaii JABSOM Medical School, Honolulu, Hawaii 96813, USA.,

    Michele Carbone & Haining Yang

  3. is at the Department of Cardiothoracic Surgery, Harvey I. Pass, New York University, New York 10016, USA.,

    Harvey I. Pass

  4. Thomas Krausz is at the Department of Pathology, University of Chicago, Illinois 60637, USA.,

    Thomas Krausz

  5. Joseph R. Testa is in the Cancer Biology Program at the Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.,

    Joseph R. Testa

Authors
  1. Michele Carbone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haining Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harvey I. Pass
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Krausz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joseph R. Testa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giovanni Gaudino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele Carbone.

Ethics declarations

Competing interests

M.C. and J.R.T. have a pending patent application on BAP1.

Related links

FURTHER INFORMATION

Michele Carbone's homepage

Glossary

Autosomal dominant

A genetic disease inherited as a result of having a single copy of the mutated gene, located on one of the 22 non-sex chromosomes.

Asbestos

Six different fibrous minerals, among about 400 present in nature, that were used commercially. Exposure to asbestos, as well as to other mineral fibres, such as erionite, can cause mesothelioma.

Uveal melanoma

(UVM). The most common primary intraocular malignancy; accounts for about 13% of melanoma deaths.

Probands

Individuals who, by seeking medical or scientific attention, allow the detection of a genetic disorder in a family.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carbone, M., Yang, H., Pass, H. et al. BAP1 and cancer. Nat Rev Cancer 13, 153–159 (2013). https://doi.org/10.1038/nrc3459

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3459

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer