TRIM3, a tumor suppressor linked to regulation of p21Waf1/Cip1

Abstract

The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell anti-viral defenses; however, roles in cancer biology are emerging. Loss of heterozygosity of the TRIM3 locus in approximately 20% of human glioblastomas raised the possibility that this NHL containing member of the TRIM gene family might be a mammalian tumor suppressor. Consistent with this, reducing TRIM3 expression increased the incidence of and accelerated the development of PDGF-induced glioma in mice. Furthermore, TRIM3 can bind to the cdk inhibitor p21WAF1/CIP1. Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15.5 and that it can block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4.