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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cell Line, Transformed
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Gene Expression Regulation, Neoplastic
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Glioblastoma / genetics
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Glioblastoma / metabolism*
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Glioblastoma / pathology
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Humans
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Immunoblotting
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Loss of Heterozygosity
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Mice
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Mice, Knockout
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Mutation
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Protein Binding
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RNA Interference
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Carrier Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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RNA, Messenger
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TRIM3 protein, human
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TRIM3 protein, mouse
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Tumor Suppressor Proteins