The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity

Mutation of the TRIM-NHL family members brat and mei-P26 in Drosophilia perturb the differentiation of transit amplifying progenitor cells resulting intumor-like phenotypes. The NHL domain is essential for their growth suppressive activity, and they can induce cell cycle exit in a RING-independentmanner. TRIM3 is the only bona fide tumor suppressor in the mammalian TRIM-NHL subfamily and like the other members of this family its ability to inhibit cell proliferation depends on the NHL domain. However, whether the RINGdomain was required for TRIM3 dependent cell cycle exit had not been investigated. Here we establish that the RING domain is required for TRIM3 induced growth suppression. Furthermore we show that this domain is necessary to promote ubiquitination of p21 in a reconstituted in vitro system whereUbcH5a is the preferred E2. Thus, the ability of TRIM3 to suppress growth isassociated with its ability to ubiquitinate proteins.

Source: BJ Signal - January 6, 2014 Category: Biochemistry Authors: R Raheja, Y Liu, E Hukkelhoven, N Yeh, A Koff Tags: BJ Signal Source Type: research