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Oncogene. 2003 May 22;22(21):3231-42.

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

Author information

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

Abstract

The newly identified p53-related gene, p73, encodes a nuclear transcription factor. Unlike p53, p73 has various isoforms with different NH(2)- and COOH-terminal tails. p73alpha 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 p73alpha, 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 p73alpha-binding proteins. The interaction was confirmed by coimmunoprecipitation experiments, whereas RACK1 did not interact with p53 or p73beta. Ectopic overexpression of RACK1 in SAOS-2 cells reduced the p73alpha-mediated transcription from the p53/p73-responsive promoters, and inhibited the p73alpha-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 p73alpha. Taken together, our observations suggest that pRB diminishes the RACK1-mediated inhibition of p73alpha activity through the interaction with RACK1.

PMID:
12761493
DOI:
10.1038/sj.onc.1206382
[Indexed for MEDLINE]

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