STAT1 is inactivated by a caspase.
Apoptosis involves the activation of a cascade of interleukin-1beta converting enzyme-like proteases (caspases), a group of cysteine proteases related to the prototype interleukin-1beta-converting enzyme (caspase-1). These proteases cleave specific intracellular targets such as poly(ADP-ribose) polymerase, DNA-dependent protein kinase, and nuclear lamins. We show here that apoptosis can be induced by double-stranded RNA. The induction of apoptosis by double-stranded RNA and other agents leads to the cleavage by a caspase of the signal transducer and activator of transcription factor, STAT1 which is pivotal in the signal transduction pathways of the interferons and many other cytokines and growth factors. The product of this cleavage is no longer able to mediate interferon-activated signal transduction and the cleavage event may play a role in regulating the apoptosis response itself.
King
P
P
Division of Biochemistry, Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, University of London, London SW17 0RE, United Kingdom.
Goodbourn
S
S
D000595:Amino Acid Sequence; D017209:Apoptosis; D020170:Caspase 1; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational; D012330:RNA, Double-Stranded / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D050794:STAT1 Transcription Factor; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013379:Substrate Specificity; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D003513:Cycloheximide; D003546:Cysteine Endopeptidases; D020170:Caspase 1