Regulation of DeltaFosB stability by phosphorylation.

The transcription factor DeltaFosB (also referred to as FosB2 or FosB[short form]) is an important mediator of the long-term plasticity induced in brain by chronic exposure to several types of psychoactive stimuli, including drugs of abuse, stress, and electroconvulsive seizures. A distinct feature of DeltaFosB is that, once induced, it persists in brain for relatively long periods of time in the absence of further stimulation. The mechanisms underlying this apparent stability, however, have remained unknown. Here, we demonstrate that DeltaFosB is a relatively stable transcription factor, with a half-life of approximately 10 h in cell culture. Furthermore, we show that DeltaFosB is a phosphoprotein in brain and that phosphorylation of a highly conserved serine residue (Ser27) in DeltaFosB protects it from proteasomal degradation. We provide several lines of evidence suggesting that this phosphorylation is mediated by casein kinase 2. These findings constitute the first evidence that DeltaFosB is phosphorylated and demonstrate that phosphorylation contributes to its stability, which is at the core of its ability to mediate long-lasting adaptations in brain.