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Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB

Oncogene volume 22, pages 3231–3242 (2003)Cite this article

Abstract

The newly identified p53-related gene, p73, encodes a nuclear transcription factor. Unlike p53, p73 has various isoforms with different NH2- and COOH-terminal tails. p73α with the longest COOH-terminal extension is most abundantly expressed in many tissues and cells among those splicing isoforms of p73 and the COOH-terminal region appears to have an autoregulatory function. To isolate and characterize the cellular protein(s) that interacts with the unique COOH-terminal region of p73α, we employed a yeast two-hybrid screen with a human fetal brain and 293 cell cDNA libraries. We identified the receptor for activated C kinase (RACK1) as a new member of p73α-binding proteins. The interaction was confirmed by coimmunoprecipitation experiments, whereas RACK1 did not interact with p53 or p73β. Ectopic overexpression of RACK1 in SAOS-2 cells reduced the p73α-mediated transcription from the p53/p73-responsive promoters, and inhibited the p73α-dependent apoptosis. On the other hand, the p53-dependent transcriptional activation as well as apoptosis was unaffected in the presence of RACK1. Furthermore, we found that pRB physically bound to RACK1, and repressed the RACK1-dependent inhibition of p73α. Taken together, our observations suggest that pRB diminishes the RACK1-mediated inhibition of p73α activity through the interaction with RACK1.

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Acknowledgements

We are grateful to Dr S Sakiyama for helpful discussion. We thank Ms A Morohashi for running the automated ABI sequencer. We thank Dr M Kitagawa for the kind gift of pRB expression plasmid. This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for a New 10-Year Strategy for Cancer Control, a Grant-in-Aid for Scientific Research on Priority Areas, and a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science, Sports and Culture, Japan.

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  1. Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba, 260-8717, Japan

    Toshinori Ozaki, Ken-ichi Watanabe, Takahito Nakagawa, Kou Miyazaki, Masato Takahashi & Akira Nakagawara

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  1. Toshinori Ozaki
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  2. Ken-ichi Watanabe
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Correspondence to Akira Nakagawara.

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Ozaki, T., Watanabe, Ki., Nakagawa, T. et al. Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB. Oncogene 22, 3231–3242 (2003). https://doi.org/10.1038/sj.onc.1206382

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