Defective TNF-α-Induced Apoptosis in STAT1-Null Cells Due to Low Constitutive Levels of Caspases

Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1997-11, Vol.278 (5343), p.1630-1632
Main Authors: Kumar, Aseem, Commane, Mairead, Flickinger, Thomas W., Horvath, Curt M., Stark, George R.
Format: Article
Language:English
Subjects:
Actinomycin
Ageing, cell death
Apoptosis
Biological and medical sciences
Caspase 1
Caspase 2
Caspase 3
Caspases
Cell death
Cell Line
Cell lines
Cell mediated immunity
Cell physiology
Cells
Cellular biology
Cellular signal transduction
Cysteine Endopeptidases - genetics
Cysteine Endopeptidases - metabolism
Dactinomycin - pharmacology
Delta cells
Dimerization
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epithelial cells
Family (Sociological Unit)
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic
Genes
Humans
Ice
Interferon-gamma - pharmacology
Messenger RNA
Molecular and cellular biology
Molecular biology
Phosphorylation
Physiological aspects
Point Mutation
Protein research
Proteins - genetics
Proteins - metabolism
Signal Transduction
STAT1 Transcription Factor
Trans-Activators - chemistry
Trans-Activators - genetics
Trans-Activators - metabolism
Transfection
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells are resistant to apoptosis by tumor necrosis factor α (TNF-α). Reintroduction of STAT1α restored both TNF-α-induced apoptosis and the expression of Ice, Cpp32, and Ich-1. Variant STAT1 proteins carrying point mutations that inactivate domains required for STAT dimer formation nevertheless restored protease expression and sensitivity to apoptosis, indicating that the functions of STAT1 required for these activities are different from those that mediate induced gene expression.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.278.5343.1630