Rel blocks both anti-Fas- and TNF alpha-induced apoptosis and an intact Rel transactivation domain is essential for this effect.
The v-Rel oncoprotein must be continuously expressed to prevent the apoptosis of transformed lymphoid cells, and also inhibits TNF alpha-induced cell death. A tetracycline-regulated cell system was used to characterize the functions necessary for the anti-apoptotic activity of Rel proteins. v-Rel mutants defective for DNA binding or transactivation showed no protective effect. Similarly, whereas the transcription-competent c-Rel and RelA proteins inhibited TNF alpha-induced cytolysis, the transactivation-negative p50/NF-kappa B1 did not. Importantly, this study is the first to show that c-Rel can also confer significant protection from Fas-mediated cell death. Since the TNFR1- and Fas-signaling pathways involve some intermediates that are common and others that are unique to each pathway, these findings indicate that c-Rel may regulate the expression of genes that function to antagonize either or both death-signaling pathways.
Zong
W X
WX
Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854-5638, USA.
Bash
J
J
Gélinas
C
C
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D020572:Oncogene Proteins v-rel; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D020569:Proto-Oncogene Proteins c-rel; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000502:physiology*; D013753:Tetracycline Resistance / Q000235:genetics; D051996:Transcription Factor RelA; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D016328:NF-kappa B; D020572:Oncogene Proteins v-rel; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D015682:Retroviridae Proteins, Oncogenic; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D004247:DNA