A role for AP-1 in apoptosis: the case for and against.
The nuclear transcription factor AP-1, composed of dimers of Fos and Jun proteins, has been linked to a startling breadth of cellular events including cell transformation, proliferation, differentiation and apoptosis. AP-1 is often portrayed as a general, nuclear decision-maker that determines life or death cell fates in response to extracellular stimuli. However, it is increasingly clear that the cellular context is critical for determining the contribution of AP-1 to cellular fates, and the role of AP-1 in apoptosis should be considered within the context of a complex network of nuclear factors that respond simultaneously to a wide range of signal transduction pathways. We take a closer look at the evidence for and against a role for AP-1 in inducing apoptosis, drawing on examples of studies in neurons, lymphocytes and hepatocytes. Although AP-1 activation is associated with a large number of apoptotic scenarios, its role in ensuring cell survival seems equally important. It is, therefore, difficult to convict AP-1 as a killer without taking into account the cellular and extracellular context within which it is functioning. Defining the target genes regulated by AP-1 in these different contexts will help to decipher the contribution of AP-1 to cell fate decisions.
Department of Developmental Biology, Fernbach Building, Institut Pasteur, 25, rue du Docteur-Roux, 75724 Paris cedex 15, France.
M
M
Ameyar
M
M
Wisniewska
J B
JB
Weitzman
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases