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Bovine GCs were used as an in vitro model, and tandem mass tag-based quantitative proteomics was performed to identify differentially expressed proteins (DEPs) following CART treatment. CART significantly downregulated clusterin (CLU), the most altered DEP (P\u2009&amp;lt;\u20090.05). Functional studies demonstrated that CLU knockdown, mimicking CART action, significantly promoted GC apoptosis, as evidenced by increased Annexin V and PI fluorescence signals (all P\u2009&amp;lt;\u20090.05). CLU knockdown also significantly suppressed proliferation, with cell viability reduced by approximately 19\u201320% compared to controls in the CCK-8 assay (P\u2009&amp;lt;\u20090.05). CLU knockdown decreased the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL, P\u2009&amp;lt;\u20090.05) and cell-cycle regulators cyclin D2 (CCND2, P\u2009&amp;lt;\u20090.05), cyclin-dependent kinase 1 (CDK1, P\u2009&amp;lt;\u20090.05), and proliferating cell nuclear antigen (PCNA, P\u2009&amp;lt;\u20090.05), while elevating pro-apoptotic effectors BCL2-associated X (BAX, P\u2009&amp;lt;\u20090.05) and cleaved caspase-3 (CASP3, P\u2009&amp;lt;\u20090.05). However, CART co-treatment did not further exacerbate these effects (P\u2009&amp;gt;\u20090.05), indicating that CLU is a key effector molecule mediating CART\u2019s pro-apoptotic action. CART\u2019s pro-apoptotic and anti-proliferative effects on GCs likely also involve other downstream targets in the altered proteome. These results demonstrate that CART reprograms the GC proteome and that downregulation of CLU is a pivotal event driving this shift toward a pro-apoptotic and anti-proliferative state, providing insights into the protein-centric mechanisms by which CART influences GC fate.<\/jats:p>","DOI":"10.1093\/biolre\/ioag124","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:53:16Z","timestamp":1781092396000},"page":"850-865","source":"Crossref","is-referenced-by-count":1,"title":["Downregulation of CLU mediates CART-induced apoptosis and suppressed proliferation in bovine granulosa cells"],"prefix":"10.1093","volume":"115","author":[{"given":"Junli","family":"Cheng","sequence":"first","affiliation":[{"name":"College of Animal Science, Shanxi Agricultural University , Taigu, Shanxi 030801 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life 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