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Model of Pim-1 regulation on Skp2 degradation. Nonphosphorylated Skp2 binds to E3 ligase APC/CCdh1 and gets ubiquitinated (Ub) followed by proteasome-mediated degradation. Pim-1 kinase phosphorylates Skp2 on multiple sites: Ser64, Ser72, and Thr417. Furthermore, the phosphorylation of Cdh1 by Pim-1 reduces Cdh1 and APC/C interaction. Both Pim-1 actions result in decreased Skp2 ubiquitination and consequently increased Skp2 stability.
