c-Jun is the cellular counterpart of the transforming prtoein of the chicken retrovirus ASV17. Via a leucine zipper, c-Jun forms homodimers and heterodimers with Fos and other jun-related proteins which, together, comprise the AP-1 transcription factor that binds TPA response elements (TREs). c-Jun therefore mediates transcriptional regulation in response to a variety of stimulants.
c-Jun is tightly regulated posttranslationally and is phosphorylated in two distinct regions.
C-terminal phosphorylation sites lie proximal to the DNA binding domain and prevent DNA binding. Likely physiologically relevant protein kinases include GSK-3 and CK-II. These sites are dephosphorylated in response to growth stimulation and likely function to repress the activity of the factor under resting conditions. Since Jun protein is present in many types of resting cells, this provides a mechanism for rapid induction of Jun function.
c-Jun is also phosphorylated at two residues proximal to the major transactivation domain. These residues (Ser 63 and 73) are required to be phosphorylated for efficient transactivation function. The kinases responsible for this modification in vivo are the SAPK/JNKs. These kinases bind with very high affinity to a region in c-Jun termed the delta domain. This region is deleted in v-Jun. v-Jun is not phosphorylated but is transcriptionally active. Thus, binding of inactive SAPK to Jun may represent a mechanism for inhibiting the function of the transcription factor. Once activated, the SAPK will phosphorylate c-Jun and dissociate. Mutation of the phosphorylation sites prevents dissociation thus resulting in inactive c-Jun. v-Jun, on the other hand, cannot bind the kinases and so is constitutively active.
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