Programs in Molecular Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Human Oncology and Pathogenesis, New York, NY, USA.
Oncogene. 2014 Jan 16;33(3):308-15. doi: 10.1038/onc.2012.596. Epub 2013 Jan 14.
The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell antiviral defenses; however, roles in cancer biology are emerging. Loss of heterozygosity of the TRIM3 locus in ∼20% of human glioblastomas raised the possibility that this NHL-domain 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 platelet-derived growth factor -induced glioma in mice. Furthermore, TRIM3 can bind to the cdk inhibitor p21(WAF1/CIP1). Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15.5 and that it might block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4.
TRIM 家族基因在很大程度上因其在发育、分化和宿主细胞抗病毒防御中的作用而被研究;然而,它们在癌症生物学中的作用正在显现。约 20%的人类神经胶质瘤中 TRIM3 基因座的杂合性缺失提出了这样一种可能性,即该 NHL 结构域包含的 TRIM 基因家族成员可能是一种哺乳动物肿瘤抑制因子。与此一致的是,降低 TRIM3 的表达增加了血小板衍生生长因子诱导的小鼠神经胶质瘤的发生率并加速了其发展。此外,TRIM3 可以与细胞周期蛋白依赖性激酶抑制剂 p21(WAF1/CIP1)结合。因此,我们得出结论,TRIM3 是一种定位于染色体 11p15.5 的肿瘤抑制因子,它可能通过隔离 p21 并阻止其促进 cyclin D1-cdk4 的积累来阻止肿瘤生长。