TRIM3, a tumor suppressor linked to regulation of p21 Waf1/Cip1

Y. Liu; R. Raheja; N. Yeh; D. Ciznadija; A. M. Pedraza; T. Ozawa; E. Hukkelhoven; H. Erdjument-Bromage; P. Tempst; N. P. Gauthier; C. Brennan; E. C. Holland; A. Koff

doi:10.1038/onc.2012.596

TRIM3, a tumor suppressor linked to regulation of p21 Waf1/Cip1

Y. Liu, R. Raheja, N. Yeh, D. Ciznadija, A. M. Pedraza, T. Ozawa, E. Hukkelhoven, H. Erdjument-Bromage, P. Tempst, N. P. Gauthier, C. Brennan, E. C. Holland, A. Koff^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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.

Original language	English (US)
Pages (from-to)	308-315
Number of pages	8
Journal	Oncogene
Volume	33
Issue number	3
DOIs	https://doi.org/10.1038/onc.2012.596
State	Published - Jan 16 2014

Funding

We thank Marta Kovatcheva and other members of the Koff lab, Pengbo Zhou (Cornell University Medical School), John Petrini (MSKCC) and Hakim Djaballah (MSKCC) for comments on this manuscript, and Max Chan Liu (The Browning School) for his assistance with Id1 staining and image acquisition. This work was supported by the Memorial Sloan-Kettering Cancer Center Core Grant (P30CA08748) and grants to Andrew Koff (CA89563). Funding was also provided by the Brain Tumor Center (YL, DC) and the Golfers Against Cancer Foundation (AK).

Keywords

PDGF
TRIM3
glioma
p21
stem/progenitor

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2012.596

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title = "TRIM3, a tumor suppressor linked to regulation of p21 Waf1/Cip1",

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.",

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note = "Funding Information: We thank Marta Kovatcheva and other members of the Koff lab, Pengbo Zhou (Cornell University Medical School), John Petrini (MSKCC) and Hakim Djaballah (MSKCC) for comments on this manuscript, and Max Chan Liu (The Browning School) for his assistance with Id1 staining and image acquisition. This work was supported by the Memorial Sloan-Kettering Cancer Center Core Grant (P30CA08748) and grants to Andrew Koff (CA89563). Funding was also provided by the Brain Tumor Center (YL, DC) and the Golfers Against Cancer Foundation (AK).",

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AU - Liu, Y.

AU - Raheja, R.

AU - Yeh, N.

AU - Ciznadija, D.

AU - Pedraza, A. M.

AU - Ozawa, T.

AU - Hukkelhoven, E.

AU - Erdjument-Bromage, H.

AU - Tempst, P.

AU - Gauthier, N. P.

AU - Brennan, C.

AU - Holland, E. C.

AU - Koff, A.

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PY - 2014/1/16

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N2 - 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.

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TRIM3, a tumor suppressor linked to regulation of p21 Waf1/Cip1

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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