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.