Send to

Choose Destination
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

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


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center