Functions of p21 and p27 in the regenerating epithelial linings of the mouse small and large intestine.
The epithelial linings of the small and large intestine are rapidly turned over and provide an ideal system for exploring links between differentiation and regulation of cell cycle exit. We utilized wild type, p21-/-, p27-/- and p21/p27-/- mice to address contributions of the Cdk inhibitors p21 and p27 to proliferation and differentiation in the mouse gastrointestinal tract. We did not detect any significant differences in proliferation, and all differentiated epithelial cell lineages were represented in all four genotypes. These data indicate that p21 and p27 do not play essential roles in the regulation of normal epithelial renewal in the intestine. These Cdk inhibitors are not needed in vivo for either assembly of Cdk/Cyclin complexes that drive active proliferation, or inhibition of Cdk/Cyclin complexes during cell cycle exit. However, expression of Cyclin D2 and to a lesser degree Cyclin D3 was reduced in p27-/- and p21/p27-/- mice, indicating a unique role for p27 in the regulation of these specific D-type Cyclins in vivo. In the absence of p27, reduced levels of Cyclin D2 and D3 may help to counteract increased proproliferative signals in the intestine.
Zheng
Yu
Y
University of Illinois College of Medicine, Department of Biochemistry and Molecular Genetics, Chicago, Illinois 60607, USA.
Bie
Wenjun
W
Yang
Ruyan
R
Perekatt
Ansu O
AO
Poole
Aleksandra J
AJ
Tyner
Angela L
AL
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation; D056742:Cyclin D2; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D007420:Intestine, Large / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012038:Regeneration; D025521:Tumor Suppressor Proteins / Q000235:genetics
C486196:Ccnd2 protein, mouse; C534697:Ccnd3 protein, mouse; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27