Figure 2.

Deubiquitinating activity of UCH-L1 in cell signaling. (A) Mutual regulation between UCH-L1 and β-catenin. By downregulating the polyubiquitination of β-catenin, overexpressed UCH-L1 stabilizes β-catenin and upregulates transcription of β-catenin/TCF, further inducing the expression of oncogenes, such as c-myc, cyclin D, c-jun and survivin. TCF binds to the promoter of UCH-L1 and upregulates the translation of UCH-L1 mRNA. (B) UCH-L1 deubiquitinates IκB-α (an endogenous inhibitor of the NF-κB signaling pathway) and upregulates its expression, leading to decreased expression of NF-κB. NF-κB activation upregulates UCH-L1 expression. TCF, T cell factor; Ub, ubiquitin; UCH-L1, Ub C-terminal hydrolase-L1.