The death effector domains (DEDs) of the molluscum contagiosum virus MC159 v-FLIP protein are not functionally interchangeable with each other or with the DEDs of caspase-8

Tara Garvey; John Bertin; Richard Siegel; Michael Lenardo; Jeffrey Cohen

doi:10.1006/viro.2002.1518

The death effector domains (DEDs) of the molluscum contagiosum virus MC159 v-FLIP protein are not functionally interchangeable with each other or with the DEDs of caspase-8

Virology. 2002 Sep 1;300(2):217-25. doi: 10.1006/viro.2002.1518.

Authors

Tara Garvey¹, John Bertin, Richard Siegel, Michael Lenardo, Jeffrey Cohen

Affiliation

¹ Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1888, USA.

PMID: 12350352
DOI: 10.1006/viro.2002.1518

Abstract

The molluscum contagiosum virus (MCV) MC159 protein contains two death effector domains (DEDs) that bind to the DEDs of caspase-8 and FADD and inhibit apoptosis. We constructed MC159 truncation mutants and found that the amino-terminal region before the first DED and nearly all the carboxyl terminus after the second DED were dispensable for the antiapoptotic activity of MC159. We also engineered tandem repeats of two identical MC159 DEDs, MC159 DEDs in the reverse orientation, and MC159-caspase-8 chimeras in which a DED of MC159 was replaced with the corresponding DED of caspase-8. Each of these constructs bound to caspase-8, but was unable to bind to FADD or block apoptosis. In addition, we constructed mutants containing only a single DED of MC159. These mutants bound to both FADD and caspase-8, but could not block apoptosis or the formation of death effector filaments. Thus, the DEDs of MC159 are not functionally interchangeable with each other or with those of caspase-8.

MeSH terms

Adaptor Proteins, Signal Transducing*
Apoptosis*
CASP8 and FADD-Like Apoptosis Regulating Protein
Carrier Proteins / antagonists & inhibitors
Carrier Proteins / chemistry*
Carrier Proteins / physiology
Caspase 8
Caspase 9
Caspases / chemistry*
Caspases / physiology
Fas-Associated Death Domain Protein
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins*
Jurkat Cells
Molluscum contagiosum virus / chemistry*
Molluscum contagiosum virus / physiology
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / physiology
Viral Proteins / chemistry*
Viral Proteins / physiology
fas Receptor / physiology

Substances

Adaptor Proteins, Signal Transducing
CASP8 and FADD-Like Apoptosis Regulating Protein
CFLAR protein, human
Carrier Proteins
FADD protein, human
Fas-Associated Death Domain Protein
Intracellular Signaling Peptides and Proteins
Tumor Necrosis Factor-alpha
Viral Proteins
fas Receptor
CASP8 protein, human
CASP9 protein, human
Caspase 8
Caspase 9
Caspases