Role of the Ubiquitin-Proteasome Pathway in Regulating Abundance of the Cyclin-Dependent Kinase Inhibitor p27

The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found to be degraded by the ubiquitin-proteasome pathway. The human ubiquitin-conjugating enzymes Ubc2 and Ubc3 were specifically involved in the ubiquitination of p27. Compared with...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1995-08, Vol.269 (5224), p.682-685
Main Authors: Pagano, Michele, Tam, Sun W., Theodoras, Anne M., Beer-Romero, Peggy, Del Sal, Giannino, Chau, Vincent, Yew, P. Renée, Draetta, Giulio F., Rolfe, Mark
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Anaphase-Promoting Complex-Cyclosome
Animals
Biochemistry
Biodegradation
Biological and medical sciences
Cell cycle
Cell Cycle Proteins
Cell cycle, cell proliferation
Cell Line
Cell physiology
Cellular biology
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases - antagonists & inhibitors
Cysteine Endopeptidases - metabolism
Electroporation
Enzyme Inhibitors - metabolism
Enzymes
Fibroblasts
Fundamental and applied biological sciences. Psychology
Half lives
Humans
Immunoblotting
Kinetics
Leupeptins - pharmacology
Ligases - metabolism
Mammals
Mice
Microtubule-Associated Proteins - metabolism
Molecular and cellular biology
Multienzyme Complexes - metabolism
Peptides
Proteasome Endopeptidase Complex
Proteins
Rabbits
Reaction products
Recombinant Proteins - metabolism
Succinates - pharmacology
Tumor Cells, Cultured
Tumor Suppressor Proteins
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligase Complexes
Ubiquitin-Protein Ligases
Ubiquitins
Ubiquitins - metabolism
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Summary:The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found to be degraded by the ubiquitin-proteasome pathway. The human ubiquitin-conjugating enzymes Ubc2 and Ubc3 were specifically involved in the ubiquitination of p27. Compared with proliferating cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity, which accounted for the marked increase of p27 half-life measured in these cells. Thus, the abundance of p27 in cells is regulated by degradation. The specific proteolysis of p27 may represent a mechanism for regulating the activity of cyclin-dependent kinases.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.7624798