Cyclin A-cdc2 kinase does not trigger but delays cyclin degradation in interphase extracts of amphibian eggs.
Purified cyclin B-cdc2 kinase has been shown previously to trigger cyclin degradation in interphase frog extracts by initiating a cascade of reactions that includes cyclin ubiquitinylation and ends with proteolysis. However, cyclin A-cdc2 kinase was not assayed in these early experiments. Here we have shown that full-length recombinant human cyclin A failed to induce cyclin degradation when it was added to frog extracts free of cyclin B, although it formed an active kinase complex with Xenopus cdc2. A highly purified kinase complex containing a truncated human cyclin A and starfish cdc2 also failed to switch on the cyclin degradation pathway. In contrast, both recombinant cyclin B and highly purified cyclin B-cdc2 kinase readily triggered degradation of both cyclins B and A in frog extracts. Whilst free cyclin A had no inhibitory effect, cyclin A-cdc2 kinase delayed degradation of both cyclins A and B induced by cyclin B-cdc2 kinase. The finding that cyclin A-cdc2 kinase cannot turn on, and even delays, cyclin destruction may be essential to prevent premature inactivation of MPF (maturation-promoting factor) before complete condensation of chromosomes and formation of the metaphase spindle.
Lorca
T
T
Centre National de la Recherche Scientifique et Institut National de la Recherche Médicale, Montpellier, France.
Labbé
J C
JC
Devault
A
A
Fesquet
D
D
Strausfeld
U
U
Nilsson
J
J
Nygren
P A
PA
Uhlen
M
M
Cavadore
J C
JC
Dorée
M
M
D000818:Animals; D016203:CDC2 Protein Kinase / Q000494:pharmacology / Q000502:physiology*; D002457:Cell Extracts / Q000737:chemistry / Q000502:physiology*; D002474:Cell-Free System; D016213:Cyclins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007399:Interphase / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D010063:Ovum / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D013215:Starfish; D014981:Xenopus / Q000378:metabolism
D002457:Cell Extracts; D016213:Cyclins; D016203:CDC2 Protein Kinase