Ubiquitination and proteasome mediated degradation of polo-like kinase.
Polo-like kinase (Plk) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Plk protein levels are low or undetectable in terminally differentiated cells and tissues and its expression is strongly correlated with cell growth. Plk protein and enzymatic activity are regulated by multiple mechanisms during cell cycle progression. During G1 Plk levels are low but increasing amounts of protein are detected during S phase and the highest amounts during G2M. Transcription of Plk message is specifically repressed during G1 but that cannot entirely account for the rapid disappearance of Plk protein at the end of mitosis. In this report we show that Plk protein can be degraded in vitro by partially purified proteasomes and that specific proteasome inhibitors can block Plk protein degradation both in vitro and in vivo. We also detected high molecular weight polyubiquitinated forms of Plk by immunoprecipitation and immunoblotting and confirmed that Plk, like other mitotic regulators, is targeted for destruction at the end of mitosis through the ubiquitin-proteasome mediated degradation pathway.
Ferris
D K
DK
Intramural Research Support Program, SAIC Frederick, Frederick, Maryland, 21702-1201, USA. Ferris@mail.ncifcrf.gov
Maloid
S C
SC
Li
C C
CC
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002474:Cell-Free System; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008938:Mitosis; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012156:Reticulocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014452:Ubiquitins; D000097869:Polo-Like Kinase 1