Both cyclin A delta 60 and B delta 97 are stable and arrest cells in M-phase, but only cyclin B delta 97 turns on cyclin destruction.
Previous work has established that destruction of cyclin B is necessary for exit from mitosis and entry into the next interphase. Sea urchin cyclin B lacking an N-terminal domain is stable, permanently activates cdc2 kinase, resulting in mitotic arrest, and permanently activates the destruction pathway acting on full length cyclin B. Here we have compared the properties of clam cyclins A and B lacking related N-terminal domains. Both cyclin A delta 60 and B delta 97 bind to cdc2 kinase, keep it hyperactivated and block the completion of mitosis. By adding purified delta cyclin proteins to a cell-free system at different cell cycle times, we find that when the cell-free system reaches the cyclin destruction point in the presence of either A delta 60 or B delta 97, the cyclin destruction pathway acting on full length cyclins fails to be turned off. However, the two cyclins differ dramatically in their ability to turn on cyclin destruction. When added to emetine-arrested interphase lysates devoid of endogenous cyclins, only cyclin B delta 97 activates the cyclin destruction system; cyclin A delta 60 does not. This functional difference between the two cyclin types, the first to be described, provides strong support for the idea that the two cyclins have different roles in the cell cycle and suggests that one specialized role of the cyclin B-cdc2 complex is to activate the cyclin destruction pathway and drive cells into interphase of the next cell cycle.
Luca
F C
FC
Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, MA 02115.
Shibuya
E K
EK
Dohrmann
C E
CE
Ruderman
J V
JV
D000818:Animals; D049872:Bivalvia; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002474:Cell-Free System; D016213:Cyclins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D015870:Gene Expression; D008845:Microinjections; D008938:Mitosis; D014981:Xenopus
D016213:Cyclins; D016203:CDC2 Protein Kinase