Science · 1995 · 376 citations · 39 references
Life SciencesCell BiologyMolecular BiologyCell CycleCell ProliferationOncogenesCell Cycle ControlCell Cycle TransitionsCell-cycle ProgressionCell-cycle RegulationCyclin-dependent KinasesRas Family OncogenesCell Cycle InhibitionCell Growth RegulationCyclin D RegulationCyclin-dependent Kinase 4 ControlCyclin-dependent Kinase RegulationOncogenic Ras MutationsOncogenic Ras SignalingP16 Expression
The cyclin-dependent kinase 4 (CDK4) regulates progression through the G1 phase of the cell cycle. The activity of CDK4 is controlled by the opposing effects of the D-type cyclin, an activating subunit, and p16INK4, an inhibitory subunit. Ectopic expression of p16INK4 blocked entry into S phase of the cell cycle induced by oncogenic Ha-Ras, and this block was relieved by coexpression of a catalytically inactive CDK4 mutant. Expression of p16INK4 suppressed cellular transformation of primary rat embryo fibroblasts by oncogenic Ha-Ras and Myc, but not by Ha-Ras and E1a. Together, these observations provide direct evidence that p16INK4 can inhibit cell growth.
39
p21 is a universal inhibitor of cyclin kinases
Yue Xiong, Gregory J. Hannon, Hui Zhang et al. · Nature · 1993 · 3.4K citations
A Cell Cycle Regulator Potentially Involved in Genesis of Many Tumor Types
Alexander Kamb, Nelleke A. Gruis, Jane Weaver-Feldhaus et al. · Science · 1994 · 2.8K citations