Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type 
E3 ligase complex and a well-characterized tumor suppressor that targets 
numerous oncoproteins for destruction. Genomic deletion or mutation of FBW7 has 
been frequently found in various types of human cancers; however, little is 
known about the upstream signaling pathway(s) governing Fbw7 stability and 
cellular functions. Here we report that Fbw7 protein destruction and tumor 
suppressor function are negatively regulated by the prolyl isomerase Pin1. Pin1 
interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 
self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. 
Consequently, overexpressing Pin1 reduces Fbw7 abundance and suppresses Fbw7's 
ability to inhibit proliferation and transformation. By contrast, depletion of 
Pin1 in cancer cells leads to elevated Fbw7 expression, which subsequently 
reduces Mcl-1 abundance, sensitizing cancer cells to Taxol. Thus, Pin1-mediated 
inhibition of Fbw7 contributes to oncogenesis, and Pin1 may be a promising drug 
target for anticancer therapy.