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The number and position of ubiquitin molecules bound to substrates' lysine residues and the number and position of ubiquitin molecules in polyubiquitin chains determine the astonishing substrate specificity of ubiquitin\u2010mediated proteolysis. Ubiquitin is likely to be expressed in mammalian gametes and embryos at any given developmental step, but the information on ubiquitin dependence of gametogenesis and fertilization is sketchy. Ubiquitin ligases E1, E2, E3, and UBC4 are active in the testis. Ubiquitin and proteasomal subunits can be detected in the human sperm centrosome that undergoes dramatic reduction during spermatid elongation. Spermatid histones are ubiquitinated as they are being transiently replaced by transitional proteins and permanently by protamines. Ubiquitin tagging of the sperm mitochondrial membranes may serve as a death sentence for paternal mitochondria at fertilization, thus promoting the maternal inheritance of mitochondrial DNA (mtDNA) in mammals. The defective spermatozoa become surface\u2010ubiquitinated during sperm descent down the epididymis. Finally, new evidence suggests the involvement of ubiquitin\u2010proteasome pathway in the zona penetration by the acrosome\u2010reacted spermatozoon. Such differential patterns of ubiquitination in the testis and epididymis, and inside the egg, may be necessary for reproductive success in humans and animals. Deciphering and eventually manipulating the ubiquitin\u2010dependent proteolysis in the reproductive system could allow us to redirect the mode of mtDNA inheritance after cloning and ooplasmic transplantation, provide germ line therapy in some cases of male infertility, develop new contraceptives, manage polyspermia during in vitro fertilization, and establish objective markers for infertility diagnostics, semen evaluation, and prediction of future fertility. Microsc. Res. Tech. 61:88\u2013102, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jemt.10319","type":"journal-article","created":{"date-parts":[[2003,3,28]],"date-time":"2003-03-28T07:54:08Z","timestamp":1048838048000},"page":"88-102","source":"Crossref","is-referenced-by-count":250,"title":["Ubiquitin\u2010dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: Killing three birds with one stone"],"prefix":"10.1002","volume":"61","author":[{"given":"Peter","family":"Sutovsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,3,27]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2500883"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1988.tb01056.x"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1989.tb00066.x"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13859"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2524"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0093-691X(99)00170-3"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.9155"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(99)00060-X"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03343782"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-3472(88)80178-7"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35057267"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0810377"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.3.513"},{"key":"e_1_2_1_15_1","volume-title":"Abnormal morphology of bovine spermatozoa","author":"Barth AD","year":"1989"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/7.1.102"},{"key":"e_1_2_1_17_1","first-page":"7","volume-title":"The spermatozoon","author":"Bedford JM","year":"1979"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.7.4043"},{"key":"e_1_2_1_19_1","first-page":"129","article-title":"Localization of a proteasomal antigen in human spermatozoa: immunohistochemical electron microscopic study","volume":"39","author":"Bialy LP","year":"2001","journal-title":"Folia Histochem Cytobiol"},{"key":"e_1_2_1_20_1","volume-title":"Promiscuity. 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