Skip to main content
SpringerLink
Log in

Topological Analysis of Cancer Protein Subnetwork in Deubiquitinase (DUB) Interactome

  • Conference paper
  • First Online:
Bioinformatics and Biomedical Engineering (IWBBIO 2020)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 12108))

  • 1628 Accesses

Abstract

Ubiquitination pathway regulates many cellular events that underlie the development of various cancer types. This led to tremendous interest in exploration of cancer therapeutics potential among the ubiquitination components, the E1, E2, E3 and deubiquitinase (DUB). Approximately 101 DUBs are encoded in human cell and often, studies on the DUBs were performed individually. Therefore, this study is conducted to observe the peculiarities of cancer protein subnetwork within DUB interactome, aiming to increase understanding on the relationship between DUBs and cancer from system biology point of view. To construct the DUB interactome, proteins associated with DUBs were extracted from IMEx consortium database and the interaction network were visualized in Cytoscape. Cancer protein nodes were identified according to the list from COSMIC Cancer Gene Census database and were extracted to form a subnetwork of 247 nodes and 326 edges. Some DUBs such as BAP1, TNFAIP3, USP6, CYLD and USP44 are observed to be the cancer proteins themselves and 78 DUBs have direct association with cancer related proteins. Topological analysis by NetworkAnalyzer and CentiScaPe suggested that OTUB1, COPS5 and USP7 have the strongest characteristics, indicating that these DUBs must have important roles in cancer-related pathways. Comparison with essential protein subnetwork suggested that the cancer protein subnetwork tends to have weaker clustering coefficient, lower betweenness centrality and higher closeness centrality. Overall, it could be said that the topological analysis of cancer protein subnetwork in DUB interactome interpreted from this study helps to provide a deeper understanding on the biological significance of DUBs in cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    Ubiquitin specific protease.

  2. 2.

    Ovarian tumour protease.

  3. 3.

    Machado-Josephin domain.

  4. 4.

    Ubiquitin C-terminal hydrolase.

  5. 5.

    Jab1/MPN/MOV34 metalloenzyme.

  6. 6.

    Zinc finger with UFM1 specific peptidase domain.

  7. 7.

    Motifs interacting with Ub-containing novel DUB family.

  8. 8.

    UniProt: UNIversal PROTein (https://www.uniprot.org/uniprot/).

  9. 9.

    PSICQUIC: Proteomics Standard Initiative Common QUery InterfaCe.

  10. 10.

    MINT: Molecular INTeraction.

  11. 11.

    IMEx: International Molecular EXchange.

  12. 12.

    COSMIC: Catalogue of Somatic Mutations in Cancer (https://cancer.sanger.ac.uk/census).

  13. 13.

    OGEE: Online GEne Essentiality database (http://ogee.medgenius.info/browse/).

References

  1. Stelzl, U., et al.: A human protein-protein interaction network: a resource for annotating the proteome. Cell 122(6), 957–968 (2005)

    Article  CAS  PubMed  Google Scholar 

  2. Ryan, D.P., Matthews, J.M.: Protein-protein interactions in human disease. Curr. Opin. Struct. Biol. 15(4), 441–446 (2005)

    Article  CAS  PubMed  Google Scholar 

  3. Harun, S., Zulkifle, N.: Construction and analysis of protein-protein interaction network to identify the molecular mechanism in laryngeal cancer. Sains Malays. 47(12), 2933–2940 (2018)

    Article  CAS  Google Scholar 

  4. Zulkifle, N., Che Rosli, A.F., Abdul Razak, S.R.: Bioinformatics analysis of differentially expressed genes in liver cancer for identification of key genes and pathways. Malaysian J. Med. Health Sci. 15(SP2), 18–24 (2019)

    Google Scholar 

  5. Weissman, A.M.: Themes and variations on ubiquitylation. Nat. Rev. Mol. Cell Biol. 2(3), 169–178 (2001)

    Article  CAS  PubMed  Google Scholar 

  6. Wilkinson, K.: Regulation of ubiquitin dependent processes by deubiquitinating enzymes. FASEB J. 11(14), 1245–1256 (1997)

    Article  CAS  PubMed  Google Scholar 

  7. Komander, D., et al.: Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell Biol. 10(8), 550–563 (2009)

    Article  CAS  PubMed  Google Scholar 

  8. Reyes-Turcu, F.E., et al.: Regulation and cellular roles of ubiquitin specific deubiquitinating enzymes. Annu. Rev. Biochem. 78, 363–397 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. Nijman, S.N.B., et al.: A genomic and functional inventory of deubiquitinating enzymes. Cell 123(5), 773–786 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. Abdul Rehman, S.A., et al.: MINDY 1 is a member of an evolutionarily conserved and structurally distinct new family of deubiquitinating enzymes. Mol. Cell 63, 146–155 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maurer, T., Wertz, I.E.: Length matters: MINDY is a new deubiquitinase family that preferentially cleaves long polyubiquitin chains. Mol. Cell 63, 4–6 (2016)

    Article  CAS  PubMed  Google Scholar 

  12. Keusekkoten, K., et al.: OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1 linked polyubiquitin. Cell 153(6), 1312–1326 (2013)

    Article  Google Scholar 

  13. Kwasna, D., et al.: Discovery and characterization of ZUFSP/ZUP1, a distinct deubiquitinase class important for genome stability. Mol. Cell 70, 150–164 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. He, M., et al.: Emerging role of DUBs in tumor metastasis and apoptosis: therapeutic implication. Pharmacol. Ther. 177, 96–107 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shannon, P., et al.: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13(11), 2498–2504 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Millán, P.P.: Visualization and analysis of biological networks. Methods Mol. Biol. 1021, 63–88 (2013)

    Article  PubMed  Google Scholar 

  17. Kerrien, S., et al.: IntAct–open source resource for molecular interaction data. Nucleic Acids Res. 35(Database issue), D561–D565 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. Chatr-aryamontri, A., et al.: MINT: the Molecular INTeraction database. Nucleic Acids Res. 35(Database issue), D572–D574 (2007)

    Article  CAS  PubMed  Google Scholar 

  19. Orchard, S., et al.: Protein interaction data curation: the International Molecular Exchange (IMEx) consortium. Nat. Methods 9(4), 345–350 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sondka, Z., et al.: The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat. Rev. Cancer 18(11), 696–705 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen, W.H., et al.: OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines. Nucleic Acids Res. 45(D1), D940–D944 (2017)

    Article  CAS  PubMed  Google Scholar 

  22. Assenov, Y., et al.: Computing topological parameters of biological networks. Bioinformatics 24(2), 282–284 (2007)

    Article  PubMed  Google Scholar 

  23. Scardoni, G., et al.: Analyzing biological network parameters with CentiScaPe. Bioinformatics 25(21), 2857–2859 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tosadori, G., et al.: Creating, generating and comparing random network models with NetworkRandomizer [version 3]. F1000Res. 5, 2524 (2017)

    Article  PubMed Central  Google Scholar 

  25. Zulkifle, N., Zulkifli, N.W.: Understanding human deubiquitinases target specificity by network based analysis towards their development as therapeutics target. In: Proceedings of the 9th International Conference on Computational Systems Biology and Bioinformatics (CSBio 2018), pp. 1–5. ACM, New York (2018)

    Google Scholar 

  26. Vidal, M., et al.: Interactome networks and human disease. Cell 144, 986–998 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Freeman, L.C.: A set of measures of centrality based on betweenness. Sociometry 40(1), 35–41 (1977)

    Article  Google Scholar 

  28. Beauchamp, M.A.: An improved index of centrality. Behav. Sci. 10, 161–163 (1965)

    Article  CAS  PubMed  Google Scholar 

  29. Zulkifle, N.: Systematic yeast two hybrid analysis of human E2 ubiquitin conjugating enzyme and deubiquitin (DUB) protein interactions. Int. J. Biol. Chem. 7(1), 1–14 (2013)

    Article  Google Scholar 

  30. Juang, Y.C., et al.: OTUB1 co-opts Lys48 linked ubiquitin recognition to suppress E2 enzyme function. Mol. Cell 45(3), 384–397 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Saldana, M., et al.: Otubain 1: a non-canonical deubiquitinase with an emerging role in cancer. Endocr. Relat. Cancer 26(1), R1–R14 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guohong, L., et al.: Jab1/COPS5 as a novel biomarker for diagnosis, prognosis, therapy prediction and therapeutic tools for human cancer. Front. Pharmacol. 9, 135 (2018)

    Article  Google Scholar 

  33. Wang, Z., et al.: USP7: novel drug target in cancer therapy. Front. Pharmacol. 10, 427 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgement

This work was supported by Universiti Sains Malaysia under Bridging Grant (304/CIPPT/6316203).

Author information

Authors and Affiliations

  1. Cluster for Oncological and Radiological Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Bertam, Penang, Malaysia

    Nurulisa Zulkifle

Authors
  1. Nurulisa Zulkifle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nurulisa Zulkifle .

Editor information

Editors and Affiliations

  1. University of Granada, Granada, Spain

    Ignacio Rojas

  2. University of Granada, Granada, Spain

    Olga Valenzuela

  3. University of Granada, Granada, Spain

    Fernando Rojas

  4. University of Granada, Granada, Spain

    Luis Javier Herrera

  5. University of Chicago and Fundacion Progreso y Salud, Granada, Spain

    Francisco Ortuño

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Zulkifle, N. (2020). Topological Analysis of Cancer Protein Subnetwork in Deubiquitinase (DUB) Interactome. In: Rojas, I., Valenzuela, O., Rojas, F., Herrera, L., Ortuño, F. (eds) Bioinformatics and Biomedical Engineering. IWBBIO 2020. Lecture Notes in Computer Science(), vol 12108. Springer, Cham. https://doi.org/10.1007/978-3-030-45385-5_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-45385-5_23

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-45384-8

  • Online ISBN: 978-3-030-45385-5

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Search

Navigation