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Skp2 E3 ligase can target various proteins, such as p27, for proteasome-mediated degradation. However, Skp2 can also function independently of its E3 ligase activity. Skp2 can be phosphorylated by Akt and promote cell migration and metastasis. In addition, Skp2 can recruit Miz1 and p300 and form a transcriptional complex of Myc-Skp2-Miz1-p300 to regulate RhoA expression. Such activities of Skp2 do not require its E3 ligase activity.
