Investigating the Caspase Cleavage of the JunB Transcription Factor

Abstract

The activation of caspases is an important step not only in apoptosis induction, but in cellular processes such as proliferation, differentiation, and the immune response. Here, we show that the AP-1 family transcription factor JunB is cleaved and dephosphorylated in a caspase-dependent manner in apoptotic cells. We demonstrate that JunB is cleaved directly by caspases, and identify aspartate 137 as the cleavage site. JunB cleavage separates the amino-terminal transactivation and carboxy-terminal DNA binding/dimerization domains to disrupt JunB transcriptional activity. Moreover, the carboxy-terminal cleavage fragment retains DNA binding activity, and the ability to dimerize with AP-1 proteins. This fragment interferes with full-length JunB binding to AP-1 sites and inhibits AP-1–dependent transcription. Finally, we show that the carboxy-terminal cleavage fragment impairs proliferation and promotes apoptosis when overexpressed in a T-cell lymphoma cell line. In summary, our findings reveal a novel mechanism of regulating the activity of an AP-1 family transcription factor.