The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2).
p130 is a tumor suppressor of the pocket protein family whose expression is posttranscriptionally regulated and largely G0 restricted. The mechanism of down-regulation of p130 expression in proliferating cells was investigated. Our results indicate that the decline of p130 expression as G0 cells reenter the cell cycle is due to a decrease in protein stability. The enhancement of p130 turnover in late G1 and S phase compared with G0 and early G1 phase was dependent on Cdk4/6-specific phosphorylation of p130 on Serine 672, and independent of Cdk2 activity. The activity of the ubiquitin ligase complex Skp1-Cul1/Cdc53-F-box protein Skp2 (SCF(Skp2)) and the proteasome were necessary for p130 degradation. In vitro, recombinant Skp2 was able to bind hyperphosphorylated but not dephosphorylated p130. Furthermore, in vitro polyubiquitination of p130 by SCF(Skp2) was specifically dependent on phosphorylation of p130 on Serine 672. Thus, like the Cdk inhibitor p27(Kip1), p130 turnover is regulated by Cdk-dependent G1 phosphorylation leading to ubiquitin-dependent proteolysis.
SciCrunch is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to scicrunch, however this is not currently a free service.