{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:06:27Z","timestamp":1790748387132,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T00:00:00Z","timestamp":1497398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF\u20102013R1A2A2A01068302"],"award-info":[{"award-number":["NRF\u20102013R1A2A2A01068302"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Transcriptional coactivator with <jats:styled-content style=\"fixed-case\">PDZ<\/jats:styled-content>\u2010binding motif (<jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content>) directly interacts with transcription factors and regulates their transcriptional activity. Extensive functional studies have shown that <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> plays critical regulatory roles in stem cell proliferation, differentiation, and survival and also modulates the development of organs such as the lung, kidney, heart, and bone. Despite the importance of <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> in stem cell maintenance, <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> function has not yet been evaluated in spermatogenic stem cells of the male reproductive system. Here, we investigated the expression and functions of <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> in mouse testis. <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> was expressed in spermatogenic stem cells; however, its deficiency caused significant structural abnormalities, including atrophied tubules, widened interstitial space, and abnormal Leydig cell expansion, thereby resulting in lowered sperm counts and impaired fertility. Furthermore, <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> deficiency increased the level of apoptosis and senescence in spermatogenic cells and Leydig cells upon aging. The expression of senescence\u2010associated \u03b2\u2010galactosidase (<jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>\u2010\u03b2gal), secretory phenotypes, and cyclin\u2010dependent kinase inhibitors (p16, p19, and p21) significantly increased in the absence of <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> downregulation in testicular cells further increased <jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>\u2010\u03b2gal and p21 expression induced by oxidative stress, whereas <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> overexpression decreased p21 induction and prevented senescence. Mechanistic studies showed that <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> suppressed <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding activity of p53 through a direct interaction and thus attenuated p53\u2010induced p21 gene transcription. Our results suggested that <jats:styled-content style=\"fixed-case\">TAZ<\/jats:styled-content> may suppress apoptosis and premature senescence in spermatogenic cells by inhibiting the p53\u2010p21 signaling pathway, thus playing important roles in the maintenance and control of reproductive function.<\/jats:p>","DOI":"10.1111\/acel.12631","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T09:33:05Z","timestamp":1497432785000},"page":"1035-1042","source":"Crossref","is-referenced-by-count":20,"title":["Transcriptional coactivator with <scp>PDZ<\/scp>\u2010binding motif is required to sustain testicular function on aging"],"prefix":"10.1111","volume":"16","author":[{"given":"Mi Gyeong","family":"Jeong","sequence":"first","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuna","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyun","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Kyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sook","family":"Hwang","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-1955-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2009.0196"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183653"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2144\/000113764"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.3.1004-1013.2003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.05.002"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-1-52"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110955"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605266104"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-151324"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.24.6778"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod64.3.946"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2014.04.010"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041434"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00201.2007"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812-1827OC"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3876"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3823"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509109102"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3328"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312569200"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003380"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7986"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1210347"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-120-4-1615"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.11.009"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00254-07"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.03.007"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126920"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313192110"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900843200"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.606"}],"container-title":["Aging 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