Acceleration of the G1/S phase transition by expression of cyclins Dl and E with an inducible system

D Resnitzky, M Gossen, H Bujard… - Molecular and cellular …, 1994 - Am Soc Microbiol
D Resnitzky, M Gossen, H Bujard, SI Reed
Molecular and cellular biology, 1994Am Soc Microbiol
Conditional overexpression of human cyclins Bl, Dl, and E was accomplished by using a
synthetic cDNA expression system based on the Escherichia coli tetracycline repressor.
After induction of these cyclins in asynchronous Rat-1 fibroblasts, a decrease in the length of
the G 1 interval was observed for cyclins Dl and E, consistent with an acceleration of the G
1/S phase transition. We observed, in addition, a compensatory lengthening of S phase and
G 2 so that the mean cell cycle length in populations constitutively expressing these cyclins …
Abstract
Conditional overexpression of human cyclins Bl, Dl, and E was accomplished by using a synthetic cDNA expression system based on the Escherichia coli tetracycline repressor. After induction of these cyclins in asynchronous Rat-1 fibroblasts, a decrease in the length of the G 1 interval was observed for cyclins Dl and E, consistent with an acceleration of the G 1/S phase transition. We observed, in addition, a compensatory lengthening of S phase and G 2 so that the mean cell cycle length in populations constitutively expressing these cyclins was unchanged relative to those of their uninduced counterparts. We found that expression of cyclin Bl had no effect on cell cycle dynamics, despite elevated levels of cyclin B-associated histone H1 kinase activity. Induction of cyclins Dl and E also accelerated entry into S phase for synchronized cultures emerging from quiescence. However, whereas cyclin E exerted a greater effect than cyclin Dl in asynchronous cycling cells, cyclin Dl conferred a greater effect upon stimulation from quiescence, suggesting a specific role for cyclin Dl in the G 0-to-G 1 transition. Overexpression of cyclins did not prevent cells from entering into quiescence upon serum starvation, although a slight delay in attainment of quiescence was observed for cells expressing either cyclin Dl or cyclin E. These results suggest that cyclins Dl and E are rate-limiting activators of the G 1-to-S phase transition and that cyclin Dl might play a specialized role in facilitating emergence from quiescence.
American Society for Microbiology