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Functions of E3 Ubiquitin Ligase Hyd in Drosophila Tissues

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Abstract—

The ubiquitin–proteasome system (UPS) is an important regulator of the main cellular processes. The components of the UPS are involved in the regulation of the cell cycle, signal transduction, the cell response to DNA damage, metabolism, and transcription control. E3 ubiquitin ligases (the enzymes that covalently attaches ubiquitin to target proteins) play a key role in the functioning of the UPS. The Drosophila tumor suppressor Hyd (hyperplastic discs) is one of the most interesting E3 ligases; it is required for the regulation of proliferation, growth, and cell differentiation. The study of hyd mutations in different tissues of Drosophila demonstrated that depending on the cellular context, Hyd can not only perform proteolytic functions associated with protein degradation, but can also, interacting with other proteins and/or nucleic acids, act as an important regulator of cellular processes.

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REFERENCES

  1. Finley D. 2009. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem. 78, 477–513.

    Article  CAS  Google Scholar 

  2. Schnell J.D., Hicke L. 2003. Non-traditional functions of ubiquitin and ubiquitin binding proteins. J. Biol. Chem. 278, 35857–35860.

    Article  CAS  Google Scholar 

  3. Mukhopadhyay D., Riezman H. 2007. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science. 315, 201–205.

    Article  CAS  Google Scholar 

  4. Hicke L. 2001. A new ticket for entry into budding vesicles – ubiquitin. Cell. 106, 527–530.

    Article  CAS  Google Scholar 

  5. Kirisako T., Kamei K., Murata S., Kato M., Fukumoto H., Kanie M., Sano S., Tokunaga F., Tanaka K., Iwai K. 2006. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25 (20), 4877–4887.

    Article  CAS  Google Scholar 

  6. Pickart C.M., Fushman D. 2004. Polyubiquitin chains: polymeric protein signals. Curr. Opin. Chem. Biol. 8, 610–616.

    Article  CAS  Google Scholar 

  7. Bernassola F., Karin M., Aaron Ciechanover A., Melino G. 2008. The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell. 14, 10–21.

    Article  CAS  Google Scholar 

  8. Sun Y. 2006. E3 ubiquitin ligases as cancer targets and biomarkers. Neoplasia. 8, 645–654.

    Article  CAS  Google Scholar 

  9. Deshaies R.J., Joazeiro C.A.P. 2009. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78, 399–434.

    Article  CAS  Google Scholar 

  10. Yang Y., Fang S., Jensen J.P., Weissman A.M., Ashwell J.D. 2000. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science. 288, 874–877.

    Article  CAS  Google Scholar 

  11. Fang S., Jensen J.P., Ludwig R.L., Vousden K.H., Weissman A.M. 2000. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem. 275, 8945–8951.

    Article  CAS  Google Scholar 

  12. Deshaies R.J. 1999. SCF and cullin/RING H2-based ubiquitin ligases. Annu. Rev. Cell Dev. Biol. 15, 435–467.

    Article  CAS  Google Scholar 

  13. Chang L., Barford D. 2014. Insights into the anaphase-promoting complex: A molecular machine that regulates mitosis. Curr. Opin. Struct. Biol. 29, 1–9.

    Article  CAS  Google Scholar 

  14. Scheffner M., Nuber U., Huibregtse J.M. 1995. Protein ubiquitination involving an E1–E2–E3 enzyme ubiquitin thioester cascade. Nature. 373, 81–83.

    Article  CAS  Google Scholar 

  15. Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E. 2011. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 474, 105–108.

    Article  CAS  Google Scholar 

  16. Martin P., Martin A., Shearn A. 1977. Studies of l(3)c43hs1 a polyphasic, temperature-sensitive mutant of Drosophila melanogaster with a variety of imaginal disc defects. Dev. Biol. 55, 213–232.

    Article  CAS  Google Scholar 

  17. Mansfield E., Hersperger E., Biggs J., Shearn A. 1994. Genetic and molecular analysis of hyperplastic discs, a gene whose product is required for regulation of cell proliferation in Drosophila melanogaster imaginal discs and germ cells. Dev. Biol. 165, 507–526.

    Article  CAS  Google Scholar 

  18. Kozlov G., Nguyen L., Lin T., De Crescenzo G., Park M., Gehring K. 2007. Structural basis of ubiquitin recognition by the ubiquitin-associated (UBA) domain of the ubiquitin ligase EDD. J. Biol. Chem. 282, 35787–35795.

    Article  CAS  Google Scholar 

  19. Tasaki T., Mulder L.C., Iwamatsu A., Lee M.J., Davydov I.V., Varshavsky A., Muesing M., Kwon Y.T. 2005. A family of mammalian E3 ubiquitin ligases that contain the UBR box motif and recognize N-degrons. Mol. Cell. Biol. 25, 7120–7136.

    Article  CAS  Google Scholar 

  20. Matta-Camacho E., Kozlov G., Menade M., Gehring K. 2012. Structure of the HECT C-lobe of the UBR5 E3 ubiquitin ligase. Acta Crystallogr. F: Struct. Biol. Cryst. Commun. 68, 1158–1163.

    Article  CAS  Google Scholar 

  21. Deo R.C., Sonenberg N., Burley S.K. 2001. X-ray structure of the human hyperplastic discs protein: An ortholog of the C-terminal domain of poly(A)-binding protein. Proc. Natl. Acad. Sci. U. S. A. 98, 4414–4419.

    Article  CAS  Google Scholar 

  22. Lim N.S., Kozlov G., Chang T.C., Groover O., Siddiqui N., Volpon L., De Crescenzo G., Shyu A.B., Gehring K. 2006. Comparative peptide binding studies of the PABC domains from the ubiquitin-protein isopeptide ligase HYD and poly(A)-binding protein. Implications for HYD function. J. Biol. Chem. 281, 14376–14382.

    Article  CAS  Google Scholar 

  23. Gateff E. 1994. Tumor suppressor and overgrowth suppressor genes of Drosophila melanogaster: Developmental aspects. Int. J. Dev. Biol. 38 (4), 565–590.

    CAS  PubMed  Google Scholar 

  24. Lee J.D., Amanai K., Shearn A., Treisman J.E. 2002. The ubiquitin ligase hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms. Development. 129, 5697–5706.

    Article  CAS  Google Scholar 

  25. Pertceva J.A., Dorogova N.V., Bolobolova E.U., Nerusheva O.O., Fedorova S.A., Omelyanchuk L.V. 2010. The role of Drosophila hyperplastic discs gene in spermatogenesis. Cell Biol. Int. 34, 991–996.

    Article  CAS  Google Scholar 

  26. Flack J. E., Mieszczanek J., Novcic N., Bienz M. 2017. Wnt-dependent inactivation of the Groucho/TLE corepressor by the HECT E3 ubiquitin ligase Hyd/UBR5. Mol. Cell. 67, 181–193.

    Article  CAS  Google Scholar 

  27. Shearer R.F., Iconomou M., Watts C.K., Saunders D.N. 2015. Functional roles of the E3 ubiquitin ligase UBR5 in cancer. Mol. Cancer Res. 13, 1523–1532.

    Article  CAS  Google Scholar 

  28. Scheffner M., Kumar S. 2014. Mammalian HECT ubiquitin-protein ligases: Biological and pathophysiological aspects. Biochim. Biophys. Acta. 1843 (1), 61–74.

  29. Muñoz-Escobar J., Matta-Camacho E., Kozlov G., Gehring K. 2015. The MLLE domain of the ubiquitin ligase UBR5 binds to its catalytic domain to regulate substrate binding. J. Biol. Chem. 290 (37), 22841–22850.

    Article  Google Scholar 

  30. Qiao X., Liu Y., Prada M.L., Mohan A.K., Gupta A., Jaiswal A., Sharma M., Merisaari J., Haikala H.M., Talvinen K., Yetukuri L., Pylvänäinen J.W., Klefström J., Kronqvist P., Meinander A., et al. 2020. UBR5 is coamplified with MYC in breast tumors and encodes an ubiquitin ligase that limits MYC-dependent apoptosis. Cancer Res. 80 (7), 1414–1427.

    Article  CAS  Google Scholar 

  31. Gupta I., Singh K., Varshney N.K., Khan S. 2018. Delineating crosstalk mechanisms of the ubiquitin proteasome system that regulate apoptosis. Front. Cell. Dev. Biol. 6, 11.

    Article  Google Scholar 

  32. Matsuura K., Huang N.J., Cocce K., Zhang L., Kornbluth S. 2017. Downregulation of the proapoptotic protein MOAP-1 by the UBR5 ubiquitin ligase and its role in ovarian cancer resistance to cisplatin. Oncogene. 36 (12), 1698–1706.

    Article  CAS  Google Scholar 

  33. Wang D., Xu Q., Yuan Q., Jia M., Niu H., Liu X., Zhang J, Young C.Y., Yuan H. 2019. Proteasome inhibition boosts autophagic degradation of ubiquitinated-AGR2 and enhances the antitumor efficiency of bevacizumab. Oncogene. 38, 3458–3474.

    Article  CAS  Google Scholar 

  34. Wang G., Tang X., Chen Y., Cao J., Huang Q., Ling X., Ren W., Liu S., Wu Y., Ray L., Lin X. 2014. Hyperplastic discs differentially regulates the transcriptional outputs of Hedgehog signaling. Mech. Dev. 133, 117–125.

    Article  CAS  Google Scholar 

  35. Cammarata-Mouchtouris A., Nguyen X.H., Acker A., Bonnay F., Goto A., Orian A., Fauvarque M.O., Boutros M., Reichhart J.M., Matt N. 2020. Hyd ubiquitinates the NF-κB co-factor Akirin to operate an effective immune response in Drosophila. PLoS Pathog. 16 (4), e1008458.

    Article  Google Scholar 

  36. Su H., Meng S., Lu Y., Trombly M.I., Chen J., Lin C., Turk A., Wang X. 2011. Mammalian hyperplastic discs homolog EDD regulates miRNA-mediated gene silencing. Mol. Cell. 43 (1), 97–109.

    Article  CAS  Google Scholar 

  37. Callaghan M.J., Russell A.J., Woollatt E., Sutherland G.R., Sutherland R.L., Watts C.K. 1998. Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs. Oncogene. 17, 3479–3491.

    Article  CAS  Google Scholar 

  38. Clancy J.L., Henderson M.J., Russell A.J., Anderson D.W., Bova R.J., Campbell I.G., Choong D.Y., Macdonald G.A., Mann G.J., Nolan T., Brady G., Olopade O.I., Woollatt E., Davies M.J., Segara D., et al. EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene. 22, 5070–5081.

  39. Meissner B., Kridel R., Lim R.S., Rogic S., Tse K., Scott D.W., Moore R., Mungall A.J., Marra M.A., Connors J.M., Steidl C., Gascoyne R.D. 2013. The E3 ubiquitin ligase UBR5 is recurrently mutated in mantle cell lymphoma. Blood. 121, 3161–3164.

    Article  CAS  Google Scholar 

  40. Forbes S.A., Bhamra G., Bamford S., Dawson E., Kok C., Clements J., Menzies A., Teague J.W., Futreal P.A., Stratton M.R (2008. The catalogue of somatic mutations in cancer (COSMIC). Curr. Protoc. Hum. Genet. Ch. 10, Unit 10–11.

  41. O’Brien P.M., Davies M.J., Scurry J.P., Smith A.N., Barton C.A., Henderson M.J., Saunders D.N., Gloss B.S., Patterson K.I., Clancy J.L., Heinzelmann-Schwarz V.A., Scolyer R.A., Zeng Y., Williams E.D., Scurr L., et al. 2008. The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro. Br. J. Cancer. 98 (6), 1085–1093.

    Article  Google Scholar 

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Funding

This work was supported by the Program of Fundamental Studies on the topics 0310-2019-0005 (I.A. Galimova) and 0324-2019-0042-C-01 (N.V. Dorogova and S.A. Fedorova).

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biology, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    I. A. Galimova

  2. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    N. V. Dorogova & S. A. Fedorova

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  1. I. A. Galimova
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  2. N. V. Dorogova
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  3. S. A. Fedorova
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Correspondence to I. A. Galimova.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving human participants or animals performed by any of the authors.

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Translated by A. Barkhash

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Galimova, I.A., Dorogova, N.V. & Fedorova, S.A. Functions of E3 Ubiquitin Ligase Hyd in Drosophila Tissues. Mol Biol 55, 305–310 (2021). https://doi.org/10.1134/S0026893321020205

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