Cks1 is degraded 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.


CONCLUSIONS
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.
Hattori
Takayuki
T
Department of Biochemistry 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Kitagawa
Kyoko
K
Uchida
Chiharu
C
Oda
Toshiaki
T
Kitagawa
Masatoshi
M
D000818:Animals; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*
C093090:CKS1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D011494:Protein Kinases; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde