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Antiproliferative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB

Oncogene volume 33, pages 55–64 (2014)Cite this article

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Abstract

The regulation of mRNA deadenylation constitutes a pivotal mechanism of the post-transcriptional control of gene expression. Here we show that the antiproliferative protein Tob, a component of the Caf1–Ccr4 deadenylase complex, is involved in regulating the expression of the proto-oncogene c-myc. The c-myc mRNA contains cis elements (CPEs) in its 3′-untranslated region (3′-UTR), which are recognized by the cytoplasmic polyadenylation element-binding protein (CPEB). CPEB recruits Caf1 deadenylase through interaction with Tob to form a ternary complex, CPEB–Tob–Caf1, and negatively regulates the expression of c-myc by accelerating the deadenylation and decay of its mRNA. In quiescent cells, c-myc mRNA is destabilized by the trans-acting complex (CPEB–Tob–Caf1), while in cells stimulated by the serum, both Tob and Caf1 are released from CPEB, and c-Myc expression is induced early after stimulation by the stabilization of its mRNA as an ‘immediate-early gene’. Collectively, these results indicate that Tob is a key factor in the regulation of c-myc gene expression, which is essential for cell growth. Thus, Tob appears to function in the control of cell growth at least, in part, by regulating the expression of c-myc.

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Acknowledgements

We thank A-B Shyu for anti-Caf1 antibody. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas ‘RNA regulation’ (No. 20112006) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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  1. Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

    K Ogami, N Hosoda, Y Funakoshi & S Hoshino

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Correspondence to S Hoshino.

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Ogami, K., Hosoda, N., Funakoshi, Y. et al. Antiproliferative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB. Oncogene 33, 55–64 (2014). https://doi.org/10.1038/onc.2012.548

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