Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3416-21. Epub 2001 Feb 27.

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

Author information

1
Apoptosis/Differentiation Laboratory, Molecular and Cellular Genetic Center, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5534, University of Lyon, 69622 Villeurbanne, France.

Abstract

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.

PMID:
11248093
PMCID:
PMC30668
DOI:
10.1073/pnas.051378298
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center