Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

Maria Barna (), Aya Pusic, Ornella Zollo, Maria Costa, Nadya Kondrashov, Eduardo Rego, Pulivarthi H. Rao and Davide Ruggero ()
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Maria Barna: University of California San Francisco, Rock Hall Room 384C, 1550 Fourth Street, San Francisco, California 94158-2517, USA
Aya Pusic: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, Byers Hall Room 308E, 1700 Fourth Street, San Francisco, California 94158-2517, USA
Ornella Zollo: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, Byers Hall Room 308E, 1700 Fourth Street, San Francisco, California 94158-2517, USA
Maria Costa: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, Byers Hall Room 308E, 1700 Fourth Street, San Francisco, California 94158-2517, USA
Nadya Kondrashov: University of California San Francisco, Rock Hall Room 384C, 1550 Fourth Street, San Francisco, California 94158-2517, USA
Eduardo Rego: Center for Cell Based Therapy, Fundação Hemocentro de Ribeirão Preto, University of Sao Paulo
Pulivarthi H. Rao: Baylor College of Medicine, Houston, Texas 77030, USA
Davide Ruggero: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, Byers Hall Room 308E, 1700 Fourth Street, San Francisco, California 94158-2517, USA

Nature, 2008, vol. 456, issue 7224, 971-975

Abstract: Myc oncogenesis requires new proteins Barna et al. show that Myc-driven tumorigenesis is dependent on its ability to increase protein synthesis, as haploinsufficiency in ribosomal proteins decreases Myc-induced tumour formation. However, tumours caused by the loss of p53 were not affected. Myc stimulates cap-dependent protein translation at the expense of IRES-dependent translation, leading to the synthesis of a different set of proteins, and this effect is reversed by ribosomal protein haploinsufficiency. Of the proteins misregulated, Cdk11 is shown to be important for the effects of Myc on genomic instability that probably contributes to Myc-induced tumour formation.

Date: 2008
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DOI: 10.1038/nature07449

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