Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice.
Document Type
Article
Publication Date
2001
First Page
194
Last Page
199
JAX Source
Proc Natl Acad Sci USA 2001 Jan; 98(1):194-9.
Grant
CA8368801/CA/NCI
Abstract
D-type cyclins (cyclins D1, D2, and D3) are key components of cell cycle machinery in mammalian cells. These proteins are believed to drive cell cycle progression by associating with their kinase partners, cyclin-dependent kinases, and by directing phosphorylation of critical cellular substrates. In addition, D-cyclins play a kinase-independent role by sequestering cell cycle inhibitors p27(Kip1) and p21(Cip1). In the past, we and others generated cyclin D1-deficient mice and have shown that these mice display developmental abnormalities, hypoplastic retinas, and pregnancy-insensitive mammary glands. To test the significance of cyclin D1-p27(Kip1) interaction within a living mouse, we crossed cyclin D1-deficient mice with mice lacking p27(Kip1), and we generated double-mutant cyclin D1(-/-)p27(-/-) animals. Here we report that ablation of p27(Kip1) restores essentially normal development in cyclin D1-deficient mice. Our results provide genetic evidence that p27(Kip1) functions downstream of cyclin D1.
Recommended Citation
Geng Y,
Yu Q,
Sicinska E,
Das M,
Bronson RT,
Sicinski P.
Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice. Proc Natl Acad Sci USA 2001 Jan; 98(1):194-9.