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Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Ubiquitin-specific protease activity of USP9Y, a male infertility gene on the Y chromosome

Kyung Ho Lee A , Gyun Jee Song B , Inn Soo Kang B , Soo Woong Kim C , Jae-Seung Paick C , Chin Ha Chung A and Kunsoo Rhee A D
+ Author Affiliations
- Author Affiliations

A School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.

B Samsung Cheil Hospital, Sungkyunkwan University College of Medicine, Seoul 100-380, Korea.

C Department of Urology, College of Medicine, Seoul National University, Seoul 110-799, Korea.

D To whom correspondence should be addressed. email: rheek@snu.ac.kr

Reproduction, Fertility and Development 15(2) 129-133 https://doi.org/10.1071/RD03002
Submitted: 6 January 2003  Accepted: 7 April 2003   Published: 7 April 2003

Abstract

Deletions of USP9Y have been observed among infertile males with defective spermatogenesis. Therefore, the gene has been designated as a male infertility gene on the Y chromosome. However, it remains to be determined how male infertility results from deletions of this gene. In order to initiate an investigation into the cellular functions of USP9Y in male germ cell development, in the present study we characterized the enzymatic specificity of USP9Y. Our results show that both USP9Y and Fam, the mouse infertility protein Usp9x, possess a protease activity specific to ubiquitin. These results suggest that, through de-ubiquitination, USP9Y may stabilize a specific target protein that is important for male germ cell development.

Extra keywords: Fam


Acknowledgments

We are grateful to Drs Stephen A. Wood (University of Queensland, Brisbane, Qld, Australia) and Janice A. Fischer (University of Texas, Austin, TX, USA) for providing us with valuable cDNA samples. This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ10-PG6-01GN13-0002). KHL is supported by a BK21 Research Fellowship from the Ministry of Education and Human Resources Development.


References

Baarends, W. M. , Van der Laan, R. , and Grootegoed, J. A. (2000). Specific aspects of the ubiquitin system in spermatogenesis J. Endocrinol. Invest. 23, 597–604.
PubMed |

Baker, R. T. , Tobias, J. T. , and Varshavsky, A. (1992). Ubiquitin-specific proteases of Saccharomyces cerevisiae J. Biol. Chem. 267, 23 364–75.


Brown, G. M. , Furlong, R. A. , Sargent, C. A. , Erickson, R. P. , Longepied, G. , Mitchell, M. , Jones, M. H. , Hargreave, T. B. , Cooke, H. J. , and Affara, N. A. (1998). Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene Hum. Mol. Genet. 7, 97–107.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Cadavid, A. L. , Ginzel, A. , and Fischer, J. A. (2000). The function of the Drosophila fat facets deubiquitinating enzyme in limiting photoreceptor cell number is intimately associated with endocytosis Development 127, 1727–36.
PubMed |

Chung, C. H. , and Baek, S. H. (1999). Deubiquitinating enzymes: their diversity and emerging roles Biochem Biophys. Res. Commun. 266, 633–40.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Elliot, D. J. , and Cooke, H. J. (1997). The molecular genetics of male infertility Bioessays 19, 801–9.
PubMed |

Everett, R. D. , Meredith, M. , Orr, A. , Cross, A. , Kathoria, M. , and Parkinson, J. (1997). A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein EMBO J. 16, 1519–30.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Fischer-Vize, J. A. , Rubin, G. M. , and Lehmann, R. (1992). The fat facets gene is required for Drosophila eye and embryo development Development 116, 985–1000.
PubMed |

Foresta, C. , Ferlin, A. , Garolla, A. , Rossato, M. , Barbaux, S. , and De Bortoli, A. (1997). Y-chromosome deletions in idiopathic severe testiculopathies Endocrinol. Metab. 82, 1075–80.


Girardi, S. K. , Mielnik, A. , and Schlegel, P. N. (1997). Submicroscopic deletions in the Y chromosome of infertile men Hum. Reprod. 12, 1635–41.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Gong, L. , Kamitani, T. , Millas, S. , and Yeh, E. T. (2000). Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins J. Biol. Chem. 275, 14 212–16.


Hershko, A. , and Ciechanover, A. (1998). The ubiquitin system Annu. Rev. Biochem. 67, 425–79.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kanai-Azuma, M. , Mattick, J. S. , Kaibuchi, K. , and Wood, S. A. (2000). Co-localization of FAM and AF-6, the mammalian homologues of Drosophila faf and canoe, in mouse eye development Mech. Dev. 91, 383–6.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Kremer, J. A. , Tuerlings, J. H. , Meuleman, E. J. , Schoute, F. , Mariman, E. , Smeets, D. F. , Hoefsloot, L. H. , Braat, D. D. , and Merkus, H. M. (1997). Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from gene to clinic Hum. Reprod. 12, 687–91.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Liford, R. , Jones, A. M. , Bishop, D. T. , Thornton, J. , and Mueller, R. (1994). Case control study of whether subfertility in men is familial BMJ 309, 570–3.
PubMed |

Najmabadi, H. , Huang, V. , Yen, P. , Subbarao, M. N. , Bhasin, D. , Banaag, L. , Naseeruddin, S. , de Kretser, D. M. , Baker, H. W. , McLachlan, R. I. , Loveland, K. A. , and Bhasin, S. (1996). Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia and oligozoospermia detected using a sequence-tagged site-based mapping strategy J. Clin. Endocrinol. Metab. 81, 1347–52.
PubMed |

Pantaleon, M. , Kanai-Azuma, M. , Mattick, J. S. , Kaibuchi, K. , Kaye, P. L. , and Wood, S. A. (2001). FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development Mech. Dev. 109, 151–60.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Papa, F. , and Hochstrasser, M. (1993). The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene Nature 366, 313–19.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Park, K. C. , Kim, J. H. , Choi, E. J. , Min, S. W. , Rhee, S. , Baek, S. H. , Chung, S. S. , Bang, O. , Park, D. , Chiba, T. , Tanaka, K. , and Chung, C. H. (2002). Antagonistic regulation of myogenesis by two deubiquitinating enzymes, UBP45 and UBP69 Proc. Natl Acad. Sci. USA 99, 9733–8.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Pryor, J. L. , Kent-First, M. , Muallem, A. , Van-Bergen, A. H. , Nolten, W. E. , Meisner, L. , and Roberts, K. P. (1997). Microdeletions in the Y chromosome of the infertile men N. Engl. J. Med. 336, 534–9.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Qureshi, S. J. , Ross, A. R. , Ma, K. , Cooke, H. J. , Intyre, M. A. , Chandley, A. C. , and Hargreave, T. B. (1996). Polymerase chain reaction screening for Y chromosome microdeletions: a first step towards the diagnosis of genetically-determined spermatogenic failure in men Mol. Hum. Reprod. 2, 775–9.
PubMed |

Simoni, M. , Gromoll, J. , Dworniczak, B. , Rolf, C. , Abshagen, K. , Kamischke, A. , Carani, C. , Meschede, D. , Behre, H. M. , Horst, J. , and Nieschlag, E. (1997). Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia Fertil. Steril. 67, 542–7.
PubMed |

Schubert, U. , Anton, L. C. , Gibbs, J. , Norbury, C. C. , Yewdell, J. W. , and Bennink, J. R. (2000). Rapid degradation of a large fraction of newly synthesized proteins by proteasomes Nature 404, 770–4.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Sun, C. , Skaletsky, H. , Birren, B. , Devon, K. , Tang, Z. , Siber, S. , Oates, R. , and Page, D. C. (1999). An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y Nat. Genet. 23, 429–32.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Taya, S. , Yamamoto, T. , Kano, K. , Kawano, Y. , Iwamatsu, A. , Tsuchiya, T. , Tanaka, K. , Kanai-Azuma, M. , Wood, S. A. , Mattick, J. S. , and Kaibuchi, K. (1998). The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme J. Cell Biol. 142, 1053–62.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Taya, S. , Yamamoto, T. , Kanai-Azuma, M. , Wood, S. A. , and Kaibuchi, K. (1999). The deubiquitinating enzyme Fam interacts with and stabilizes beta-catenin Genes Cells. 4, 757–67.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Tobias, J. W. , and Varshavsky, A. (1991). Cloning and functional analysis of the ubiquitin-specific protease gene UBP1 of Saccharomyces cerevisiae.  J. Biol. Chem. 266, 12 021–8.


van der Ven, K. , Montag, M. , Peschka, B. , Leygraaf, J. , Schwanitz, G. , Haidl, G. , Krebs, D. , and van der Ven, H. (1997). Combined cytogenetic and Y chromosome microdeletion screening in males undergoing intracytoplasmic sperm injection Mol. Hum. Reprod. 3, 699–704.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Vogt, P. H. , Chandley, A. C. , Hargreave, T. B. , Keil, R. , Ma, K. , and Sharkey, A. (1992). Microdeletions in interval 6 of the Y chromosome of male with idiopathic sterility point to disruption of AZF, a human spermatogenesis gene Hum. Genet. 89, 491–6.
PubMed |

Vogt, P. H. , Edelmann, A. , Kirsch, S. , Henegariu, O. , Hirschmann, P. , Kiesewetter, F. , Kohn, F. M. , Schill, W. B. , Farah, S. , and Ramos, C. , et al. (1996). Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11 Hum. Mol. Genet. 5, 933–43.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Wilkinson, K. D. , Tashayev, V. L. , O’Connor, L. B. , Larsen, C. N. , Kasperek, E. , and Pickart, C. M. (1995). Metabolism of the polyubiquitin degradation signal: structure, mechanism, and role of isopeptidase T Biochemistry 34, 14 535–46.


Yeh, E. T. , Gong, L. , and Kamitani, T. (2000). Ubiquitin-like proteins: new wines in new bottles Gene 248, 1–14.
Crossref | GoogleScholarGoogle Scholar | PubMed |