title: Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27.
abstract: 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.
authors.affiliation: Mitotix Inc., Cambridge, MA 02139, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pagano
authors.forename: S W
authors.initials: SW
authors.lastname: Tam
authors.forename: A M
authors.initials: AM
authors.lastname: Theodoras
authors.forename: P
authors.initials: P
authors.lastname: Beer-Romero
authors.forename: G
authors.initials: G
authors.lastname: Del Sal
authors.forename: V
authors.initials: V
authors.lastname: Chau
authors.forename: P R
authors.initials: PR
authors.lastname: Yew
authors.forename: G F
authors.initials: GF
authors.lastname: Draetta
authors.forename: M
authors.initials: M
authors.lastname: Rolfe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D018274:Electroporation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008025:Ligases / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D013386:Succinates; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C063261:acetylleucyl-leucyl-norleucinal; D050760:Cyclin-Dependent Kinase Inhibitor p27; C017290:2,3-epoxysuccinic acid; D000255:Adenosine Triphosphate; C577447:CDC34 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D018844:Cyclin-Dependent Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases