Acts as a chaperone during the assbly of the 26S proteasome, specifically of the PA700,19S regulatory complex (RC). In the initial step of the base subcomplex assbly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assbles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA,ROCK,PTEN pahway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53,TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53,TP53 and the mono- and polyubiquitination of p53,TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1,CRM1-mediated nuclear export.
"Initial characterization of the human central proteome."Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.BMC Syst. Biol. 5:17-17(2011)
Research Topic:Cancer
