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Oncogene ; 33(3): 308-15, 2014 Jan 16.
Article in English | MEDLINE | ID: mdl-23318451

ABSTRACT

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.


Subject(s)
Carrier Proteins/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Glioblastoma/metabolism , Tumor Suppressor Proteins/metabolism , Animals , Carrier Proteins/genetics , Cell Line , Cell Line, Transformed , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Humans , Immunoblotting , Loss of Heterozygosity , Mice , Mice, Knockout , Mutation , Protein Binding , RNA Interference , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tumor Suppressor Proteins/genetics
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