TY - JOUR
T1 - MYBL2, a link between proliferation and differentiation in maturing colon epithelial cells
AU - Papetti, Michael
AU - Augenlicht, Leonard H.
PY - 2011/3
Y1 - 2011/3
N2 - Multiple signals, controlling both proliferation and differentiation, must be integrated in the reprogramming of intestinal epithelial cells during maturation along the crypt-luminal axis. The v-myb family member Mybl2, a molecule implicated in the development and maintenance of the stem cell phenotype, has been suggested to play an important role in proliferation and differentiation of several cell types and is a gene we have found is commonly regulated in several systems of colon cell maturation both in vitro and in vivo. Here we show that siRNA silencing of Mybl2 in proliferating Caco-2 cells increases expression of the cell-cycle regulators cdk2, cyclin D2, and c-myc and decreases expression of cdc25B and cyclin B2 with a consequent 10% increase of cells in G2/M and a complementary 10% decrease in G1. Mybl2 occupies sequences upstream of transcriptional start sites of cyclin D2, c-myc, cyclin B2, and cdc25B and regulates reporter activity driven by upstream regions of cdk2, cyclin D2, and c-myc. These data suggest that Mybl2 plays a subtle but key role in linking specific aspects of cell-cycle progression with generation of signals for differentiation and may therefore be fundamental in commitment of intestinal epithelial cells to differentiation pathways during their maturation.
AB - Multiple signals, controlling both proliferation and differentiation, must be integrated in the reprogramming of intestinal epithelial cells during maturation along the crypt-luminal axis. The v-myb family member Mybl2, a molecule implicated in the development and maintenance of the stem cell phenotype, has been suggested to play an important role in proliferation and differentiation of several cell types and is a gene we have found is commonly regulated in several systems of colon cell maturation both in vitro and in vivo. Here we show that siRNA silencing of Mybl2 in proliferating Caco-2 cells increases expression of the cell-cycle regulators cdk2, cyclin D2, and c-myc and decreases expression of cdc25B and cyclin B2 with a consequent 10% increase of cells in G2/M and a complementary 10% decrease in G1. Mybl2 occupies sequences upstream of transcriptional start sites of cyclin D2, c-myc, cyclin B2, and cdc25B and regulates reporter activity driven by upstream regions of cdk2, cyclin D2, and c-myc. These data suggest that Mybl2 plays a subtle but key role in linking specific aspects of cell-cycle progression with generation of signals for differentiation and may therefore be fundamental in commitment of intestinal epithelial cells to differentiation pathways during their maturation.
UR - http://www.scopus.com/inward/record.url?scp=78650656885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650656885&partnerID=8YFLogxK
U2 - 10.1002/jcp.22399
DO - 10.1002/jcp.22399
M3 - Article
C2 - 20857481
AN - SCOPUS:78650656885
SN - 0021-9541
VL - 226
SP - 785
EP - 791
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 3
ER -