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

Oncogene. 2003 May 22;22(21):3231-42. doi: 10.1038/sj.onc.1206382.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • COS Cells
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / metabolism
  • GTP-Binding Proteins
  • Genes, Tumor Suppressor
  • Humans
  • Mutation
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / physiology
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Precipitin Tests
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Retinoblastoma Protein / physiology*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*
  • Tumor Suppressor Proteins
  • Two-Hybrid System Techniques


  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Retinoblastoma Protein
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • GTP-Binding Proteins