TY - JOUR
T1 - Defective TNF-α-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases
AU - Kumar, Aseem
AU - Commane, Mairead
AU - Flickinger, Thomas W.
AU - Horvath, Curt M.
AU - Stark, George R.
PY - 1997/11/28
Y1 - 1997/11/28
N2 - 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.
AB - 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.
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U2 - 10.1126/science.278.5343.1630
DO - 10.1126/science.278.5343.1630
M3 - Article
C2 - 9374464
AN - SCOPUS:0030659512
SN - 0036-8075
VL - 278
SP - 1630
EP - 1632
JO - Science
JF - Science
IS - 5343
ER -