Defective TNF-α-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases

Aseem Kumar, Mairead Commane, Thomas W. Flickinger, Curt M. Horvath, George R. Stark*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

426 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1630-1632
Number of pages3
JournalScience
Volume278
Issue number5343
DOIs
StatePublished - Nov 28 1997

ASJC Scopus subject areas

  • General

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