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 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.
Pagano
M
M
Mitotix Inc., Cambridge, MA 02139, USA.
Tam
S W
SW
Theodoras
A M
AM
Beer-Romero
P
P
Del Sal
G
G
Chau
V
V
Yew
P R
PR
Draetta
G F
GF
Rolfe
M
M
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*
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