TY - JOUR
T1 - Functions of p21 and p27 in the regenerating epithelial linings of the mouse small and large intestine
AU - Zheng, Yu
AU - Bie, Wenjun
AU - Yang, Ruyan
AU - Perekatt, Ansu O.
AU - Poole, Aleksandra J.
AU - Tyner, Angela L.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Cip
KW - Colon
KW - Cyclin D2
KW - Cyclin D3
KW - Duodenum
KW - Kip
KW - p21
KW - p27
KW - p57
UR - http://www.scopus.com/inward/record.url?scp=56149124254&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56149124254&partnerID=8YFLogxK
U2 - 10.4161/cbt.7.6.5868
DO - 10.4161/cbt.7.6.5868
M3 - Article
C2 - 18344686
AN - SCOPUS:56149124254
SN - 1538-4047
VL - 7
SP - 873
EP - 879
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 6
ER -