Cell anchorage regulates apoptosis through the retinoblastoma tumor suppressor E2F pathway

被引:104
作者
Day, ML
Foster, RG
Day, KC
Zhao, X
Humphrey, P
Swanson, P
Postigo, AA
Zhang, SH
Dean, DC
机构
[1] UNIV MICHIGAN,CTR COMPREHENS CANC,ANN ARBOR,MI 48109
[2] WASHINGTON UNIV,SCH MED,DEPT MED & CELL BIOL,ST LOUIS,MO 63110
[3] WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110
关键词
D O I
10.1074/jbc.272.13.8125
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epithelial cells are dependent upon adhesion to extracellular matrix for survival. We show that loss of beta 1 integrin receptor contact with extracellular matrix signals the inhibition of G(1) cyclin-dependent kinase activity. This loss of cyclin-dependent kinase activity leads to accumulation of the hypophosphorylated (active) form of the retinoblastoma tumor suppressor protein (Rb). We present evidence that in epithelial cells deprived of matrix contact, the growth suppression signal elicited by hypophosphorylated Rb opposes stimulatory signals hom serum growth factors, leading to a cell cycle conflict that triggers apoptosis. This apoptotic pathway is modulated by Bcl-2 through a novel mechanism that regulates Rb phosphorylation. We present evidence that the Rb-dependent apoptotic pathway functions in vivo in the apoptosis of the prostate glandular epithelium following castration.
引用
收藏
页码:8125 / 8128
页数:4
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