BACKGROUND: Recent work has demonstrated the role of cdc kinase subunit 1 (Cks1) in the ubiquitin-proteasome dependent degradation of CDK inhibitor p27Kip1 protein as an essential cofactor for SCFSkp2 ubiquitin ligase. Although over-expression of Cks1 protein as well as it of Skp2 might be associated with tumour progression via p27Kip1 protein degradation, it is unknown how the cellular level of Cks1 is regulated. RESULTS: Here we show that Cks1 protein is degraded via the ubiquitin-proteasome pathway. Degradation of Cks1 protein was markedly inhibited by proteasome inhibitors. In addition, Cks1 protein was modified with polyubiquitin chains both in vivo and in vitro. Furthermore, we found that degradation of Cks1 protein via the ubiquitin-proteasome pathway was facilitated in M phase during the cell cycle. CONCLUSION: These observations suggest that the level of expression of Cks1 protein is regulated at not only the transcriptional level but also the post-translational level via the ubiquitin-proteasome pathway in a cell-cycle-dependent manner.
BACKGROUND: Recent work has demonstrated the role of cdc kinase subunit 1 (Cks1) in the ubiquitin-proteasome dependent degradation of CDK inhibitor p27Kip1 protein as an essential cofactor for SCFSkp2 ubiquitin ligase. Although over-expression of Cks1 protein as well as it of Skp2 might be associated with tumour progression via p27Kip1 protein degradation, it is unknown how the cellular level of Cks1 is regulated. RESULTS: Here we show that Cks1 protein is degraded via the ubiquitin-proteasome pathway. Degradation of Cks1 protein was markedly inhibited by proteasome inhibitors. In addition, Cks1 protein was modified with polyubiquitin chains both in vivo and in vitro. Furthermore, we found that degradation of Cks1 protein via the ubiquitin-proteasome pathway was facilitated in M phase during the cell cycle. CONCLUSION: These observations suggest that the level of expression of Cks1 protein is regulated at not only the transcriptional level but also the post-translational level via the ubiquitin-proteasome pathway in a cell-cycle-dependent manner.
Authors: Gang Zheng; Michal-Ruth Schweiger; Gustavo Martinez-Noel; Leon Zheng; Jennifer A Smith; J Wade Harper; Peter M Howley Journal: J Virol Date: 2009-06-24 Impact factor: 5.103