Regulation And Biological Functions Of The Regy Proteasome

REGγ,a member of the11s (also known as REG or PA28) proteasome activatior family, previous research found REGy can only facilitates proteasome to degrade small peptides. But recent publications challenge this traditional conception and found REGy can activate or promote the proteasome to degrade several intracellular intact proteins, such as SRC-3, p21, p16, p19, p53, smurfl, securin and HCV core protein. Those proteins involve in almost all the celluar process including apoptosis, cell growth and cell cycle regulation. Our reserch in order to future illustrate the biological functions of REGy and the potential mechanisim. We found REG y can facilitate the turnover of tumor suppressor p53by promoting MDM2-mediated p53mono-ubiquitination and nuclear export, which can underlying the mechanism REGy inhibit p53-mediated apoptosis. Also, through the yeast two hybrid system and mass spectrum technique, we identifed one REG y specific binding nuclear protein---NIP30. Its biochemical properties and biological functions are all largely unknown. We found NIP30is not the substrate of REGy but can regulate the activity and biological functions of REGγ. The REGγ substrates p21, smurfl and securin can be stablized by NIP30, and through a way inhibit the activity of REGy. We perform a series of IP to mapping the REGy binding site in NIP30. finally, it been narrowed to a serine-riched region(about12amino acid)between219and231redidues. The site mutantation strategy found the phosphorylation is required for the binding between NIP30and REGy, and also is requied for NIP30regulating the activity of REGγ.This research showed us a new and potential regulatory mechanism of REGy, which could also be a new clinic strategy and target for curing the disease which is REGy related.