Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle.
Cells deprived of serum mitogens will either undergo immediate cell cycle arrest or complete mitosis and arrest in the next cell cycle. The transition from mitogen dependence to mitogen independence occurs in the mid-to late G1 phase of the cell cycle and is called the restriction point. Murine Balb/c-3T3 fibroblasts deprived of serum mitogens accumulated the cyclin-dependent kinase (CDK) inhibitor p27Kip1. This was correlated with inactivation of essential G1 cyclin-CDK complexes and with cell cycle arrest in G1. The ability of specific mitogens to allow transit through the restriction point paralleled their ability to down-regulate p27, and antisense inhibition of p27 expression prevented cell cycle arrest in response to mitogen depletion. Therefore, p27 is an essential component of the pathway that connects mitogenic signals to the cell cycle at the restriction point.
Coats
S
S
Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Flanagan
W M
WM
Nourse
J
J
Roberts
J M
JM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D018797:Cell Cycle Proteins; D003470:Culture Media; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016193:G1 Phase; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D003470:Culture Media; D016213:Cyclins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D008934:Mitogens; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D018844:Cyclin-Dependent Kinases