Timing of cyclin D1 expression within G1 phase is controlled by Rho.
The expression of cyclin D1 in mid-G1 phase is associated with sustained ERK activity, and we show here that Rho is required for the sustained ERK signal. However, we also report that Rho inhibits an alternative Rac/Cdc42-dependent pathway, which results in a strikingly early G1-phase expression of cyclin D1. Thus, cyclin D1 is induced in mid-G1 phase because a Rho switch couples its expression to sustained ERK activity rather than Rac and Cdc42. Our results show that Rho is crucial for maintaining the correct timing of cyclin D1 expression in G1 phase and describe a new role for cytoskeletal integrity in the regulation of cell cycle progression.
Welsh
C F
CF
Department of Medicine and Sylvester Cancer Center, University of Miami School of Medicine, 1475 NW 12th Ave, Miami, Florida 33136, USA. cwelsh@med.miami.edu
Roovers
K
K
Villanueva
J
J
Liu
Y
Y
Schwartz
M A
MA
Assoian
R K
RK
D016475:3T3 Cells; D000818:Animals; D019938:Cyclin D1 / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016193:G1 Phase; D015870:Gene Expression; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors*
D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins