Abstract

The retinoblastoma binding protein 6 (RBBP6) proteins (also called P-53 Associated Cell Testis Derived (PACT)) are highly upregulated in esophageal cancer and enhance the activity of MDM2, a p53 inhibitor with ubiquitin ligase activity that is over expressed in many human cancers.  Mammalian RBBP6 binds the tumour suppressor proteins p53 and the retinoblastoma protein (Rb). The invertebrate orthologues, on the other hand, have not been shown experimentally to have these properties and they have no obvious sequence features that are similar to the mammalian p53- and Rb-binding domains. General features of RBBP6 proteins such as a highly conserved N-terminal ubiquitin-like domain and a RING-finger indicate that they may be involved in proteolytic degradation of substrate proteins via the proteasome pathway. They have recently been found to act downstream hedgehog in certain normal developmental processes. This may implicate RBBP6 proteins in a wider range of human cancers. These data imply that antagonists of RBBP6 can be used as effective antitumour agents to treat tumours that have functional p53.

Key words: p53, RBBP6, PACT, SNAMA, cell cycle, apoptosis, cancer.