The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation

被引:166
作者
Forcet, C
Ye, X
Granger, L
Corset, V
Shin, H
Bredesen, DE
Mehlen, P [1 ]
机构
[1] Buck Inst Age Res, Novato, CA 94945 USA
[2] Univ Lyon, CNRS, UMR 5534, Apoptosis Differentiat Lab,Mol & Cellular Genet C, F-69622 Villeurbanne, France
[3] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
关键词
D O I
10.1073/pnas.051378298
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The expression of DCC (deleted in colorectal cancer) is often markedly reduced in colorectal and other cancers. However, the rarity of point mutations identified in DCC coding sequences and the lack of a tumor predisposition phenotype in DCC hemizygous mice have raised questions about its role as a tumor suppressor. DCC also mediates axon guidance and functions as a dependence receptor; such receptors create cellular states of dependence on their respective ligands by inducing apoptosis when unoccupied by ligand. We now show that DCC drives cell death independently of both the mitochondria-dependent pathway and the death receptor/caspase-8 pathway. Moreover, we demonstrate that DCC interacts with both caspase-3 and caspase-9 and drives the activation of caspase-3 through caspase-9 without a requirement for cytochrome c or Apaf-1. Hence, DCC defines an additional pathway for the apoptosome-independent caspase activation.
引用
收藏
页码:3416 / 3421
页数:6
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