{"id":1926,"date":"2026-04-16T04:54:26","date_gmt":"2026-04-16T04:54:26","guid":{"rendered":"https:\/\/amm-journal.org\/?p=1926"},"modified":"2026-04-16T04:54:26","modified_gmt":"2026-04-16T04:54:26","slug":"skp2-cellular-homeostasis-cancer","status":"publish","type":"post","link":"https:\/\/amm-journal.org\/index.php\/2026\/04\/16\/skp2-cellular-homeostasis-cancer\/","title":{"rendered":"The multidimensional biology of SKP2: mechanisms, pathologies, and emerging therapeutic frontiers"},"content":{"rendered":"

Announcing a new publication for Acta Materia Medica<\/em> journal. \u00a0\u00a0S phase kinase-associated protein 2 (SKP2), the rate-limiting substrate receptor of the SKP1-Cullin1-F-box (SCF) E3 ubiquitin ligase complex, is considered a canonical gatekeeper of cell cycle progression. However, accumulating evidence indicates that SKP2 functions as a multifaceted signaling hub that orchestrates metabolic reprogramming, the DNA damage response, stem cell maintenance, and synaptic plasticity. Dysregulation of these processes contributes to the pathogenesis of many types of human diseases, including cancer. This review provides a comprehensive overview of the diverse biological roles of SKP2, beginning with detailed insights into the assembly and substrate-recognition mechanisms of the Cullin1-SKP2-CKS1 protein complex. Moreover, the functional dichotomy of SKP2 is explored, expanding its classic role in K48-linked proteasomal degradation to include noncanonical roles in K63-linked signaling activation. Furthermore, the pathogenic implications of SKP2 in malignancies such as castration-resistant prostate cancer (CRPC) and triple-negative breast cancer (TNBC) is elucidated, as well as neurodegenerative conditions, including Alzheimer\u2019s disease. More importantly, the therapeutic approaches targeting SKP2, highlighting the shift from first-generation protein-protein interaction (PPI) inhibitors to next-generation degraders are evaluated, including the novel induced-proximity degrader SKPer1 and emerging PROTACs. Finally, to bridge the gap to clinical translation, the remaining druggability challenges and future directions for pharmacological optimization are discussed.<\/p>\n

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Tao Hou, Xiangmei Hua and Peiqiang Yan et al. The multidimensional biology of SKP2: mechanisms, pathologies, and emerging therapeutic frontiers.\u00a0Acta Materia Medica.\u00a0<\/em>2026. Vol. 5(1):113-143. DOI: 10.15212\/AMM-2025-0094<\/p>\n","protected":false},"excerpt":{"rendered":"

Announcing a new publication for Acta Materia Medica journal. \u00a0\u00a0S phase kinase-associated protein 2 (SKP2), the rate-limiting substrate receptor of the SKP1-Cullin1-F-box (SCF) E3 ubiquitin ligase complex, is considered a canonical gatekeeper of cell cycle progression. However, accumulating evidence indicates that SKP2 functions as a multifaceted signaling hub that orchestrates metabolic reprogramming, the DNA damage […]<\/p>\n","protected":false},"author":5,"featured_media":1927,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[187,571,89,572],"class_list":["post-1926","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news-and-events","tag-cancer","tag-cellular-homeostasis","tag-skp2","tag-translational"],"yoast_head":"\nThe Multidimensional Biology of SKP2:<\/title>\n<meta name=\"description\" content=\"This comprehensive review systematically dissects the hierarchical functions of SKP2 in cellular regulation and pathology\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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