{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:07:27Z","timestamp":1790849247845,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Protein neddylation inactivation is a novel topic in cancer research. However, there are few studies on the mechanism of neddylation underlying the development of sheep follicular granulosa cells (GCs). In this study, the development of follicular GCs in sheep was inactivated by MLN4924, a neddylation\u2010specific inhibitor, which significantly attenuated the proliferation and cell index of sheep follicular GCs. Further, the inactivation of neddylation by MLN4924 caused the accumulation of the cullin ring ligase (CRLs) substrates Wee1 and c\u2010Myc, which could upregulate NOXA protein expression. Meanwhile, the B\u2010cell lymphoma\/leukemia 2 (BCL2) family members Bcl\u20102 and MCL\u20101 were downregulated, subsequently inducing apoptosis in follicular GCs of sheep. Increasing Wee1 levels caused G2\/M\u2010phase arrest. The effects of neddylation inactivation on Akt, the JAK2\/STAT3 signaling pathway, and Forkhead box class O(FOXO) family members were evaluated. Neddylation inactivation by MLN4924 increased the levels of phospho\u2010Akt, JAK2, phospho\u2010STAT3, and FOXO1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and decreased the levels of phospho\u2010FOXO3a and STAT3 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In addition, MLN4924 could alter the mitochondrial morphology of GCs, increase cellular glucose utilization and lactate production, increase reactive oxygen species (ROS) generation, and promote sheep follicular GCs glycolysis, thus causing changes in mitochondrial functions. Together, these findings point to an unrecognized role of neddylation in regulating follicular GCs proliferation in sheep.<\/jats:p>","DOI":"10.1002\/jcp.30777","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T07:00:46Z","timestamp":1652770846000},"page":"3278-3291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Neddylation inactivation affects cell cycle and apoptosis in sheep follicular granulosa cells"],"prefix":"10.1002","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-5052","authenticated-orcid":false,"given":"Xiaowei","family":"Qin","sequence":"first","affiliation":[{"name":"Animal Genetics, Breeding and Reproduction Laboratory, College of Animal Science Shanxi Agricultural University Taigu Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Dang","sequence":"additional","affiliation":[{"name":"Animal 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