Regulation of APC(Cdh1) E3 ligase activity by the Fbw7/cyclin E signaling axis contributes to the tumor suppressor function of Fbw7.

ABSTRACT: Fbw7 and Cdh1 are substrate-recognition subunits of the SCF- and APC-type E3 ubiquitin ligases, respectively. There is emerging evidence suggesting that both Fbw7 and Cdh1 function as tumor suppressors by targeting oncoproteins for destruction. Loss of Fbw7, but not Cdh1, is frequently observed in various human tumors. However, it remains largely unknown how Fbw7 mechanistically functions as a tumor suppressor and whether there is a signaling crosstalk between Fbw7 and Cdh1. Here, we report that Fbw7-deficient cells not only display elevated expression levels of SCF(Fbw7) substrates, including cyclin E, but also have increased expression of various APC(Cdh1) substrates. We further defined cyclin E as the critical signaling link by which Fbw7 governs APC(Cdh1) activity, as depletion of cycl

SUBMITTER: Lau AW 

PROVIDER: S-EPMC3698637 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature