Caspase-10 is an initiator caspase in death receptor signaling

doi:10.1073/pnas.241358198

Caspase-10 is an initiator caspase in death receptor signaling

^*Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive, MSC 1892, Bethesda, MD 20892; and ^‡Department of Immunology, Baylor College of Medicine, Houston, TX 77030

Edited by William E. Paul, National Institutes of Health, Bethesda, MD, and approved September 12, 2001 (received for review July 12, 2001)

Abstract

A role for caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function independently of caspase-8 in initiating Fas- and tumor necrosis factor-related apoptosis-inducing ligand-receptor-mediated apoptosis. Moreover, Fas crosslinking in primary human T cells leads to the recruitment and activation of caspase-10. Fluorescent resonance energy transfer analysis indicates that the death-effector domains of caspase-8 and -10 both interact with the death-effector domain of FADD. Nonetheless, we find that caspase-8 and -10 may have different apoptosis substrates and therefore potentially distinct roles in death receptor signaling or other cellular processes.

Footnotes

↵ † Present address: Department of Immunology, Baylor College of Medicine, Houston, TX 77030.
↵ § To whom reprint requests should be addressed. E-mail: lenardo{at}nih.gov.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

FasL,

Fas ligand;

TRAIL,

tumor necrosis factor-related apoptosis-inducing ligand;

FRET,

fluorescent resonance energy transfer;

DED,

death-effector-domain;

DR,

death receptor;

CFP,

cyan fluorescent protein;

YFP,

yellow fluorescent protein;

CID,

chemical inducer of dimerization;

FKBP,

FK506 binding protein;

PHA,

phytohemagglutinin;

DC,

dendritic cell;

GFP,

green fluorescent protein;

EBV,

Epstein–Barr virus