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

Oncogene volume 33, pages 308–315 (2014)Cite this article

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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 p21WAF1/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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Acknowledgements

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).

Author contributions: YL carried out the experiments identifying TRIM3 and measuring the effect of manipulating TRIM3 on p21 in cells. AMP, TO, NPG, CB and ECH analyzed TRIM3 expression in human tumors and human tumor extract. RR, NY, DC, EH, HEB and PT provided experimental assistance or reagents throughout the course of this work. AK directed the research.

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Authors and Affiliations

  1. Programs in Molecular Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Y Liu, R Raheja, N Yeh, D Ciznadija, E Hukkelhoven, H Erdjument-Bromage, P Tempst & A Koff

  2. Human Oncology and Pathogenesis, New York, NY, USA

    A M Pedraza & C Brennan

  3. Cancer Biology, New York, NY, USA

    T Ozawa & E C Holland

  4. Computational Biology. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    N P Gauthier

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Correspondence to A Koff.

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Liu, Y., Raheja, R., Yeh, N. et al. TRIM3, a tumor suppressor linked to regulation of p21Waf1/Cip1. Oncogene 33, 308–315 (2014). https://doi.org/10.1038/onc.2012.596

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