Dimerization and DNA-binding properties of the transcription factor DeltaFosB.

The transcription factor, DeltaFosB, a splice isoform of fosB, accumulates in rodents in a brain-region-specific manner in response to chronic administration of drugs of abuse, stress, certain antipsychotic or antidepressant medications, electroconvulsive seizures, and certain lesions. Increasing evidence supports a functional role of such DeltaFosB induction in animal models of several psychiatric and neurologic disorders. Fos family proteins, including DeltaFosB, are known to heterodimerize with Jun family proteins to create active AP-1 transcription-factor complexes, which bind to DNA specifically at AP-1 consensus sites.

Regulation of DeltaFosB transcriptional activity by Ser27 phosphorylation.

The transcription factor, DeltaFosB, is an important mediator of the long-term plasticity induced in brain by chronic exposure to drugs of abuse, stress, or several other psychoactive stimuli. We have previously demonstrated that the casein kinase 2 (CK2)-mediated phosphorylation of a highly conserved N-terminal serine (Ser27) plays a critical role in regulating DeltaFosB's unusual stability, while it does not affect that of the full-length FosB protein. In the present study, we analysed whether CK2 and Ser27 phosphorylation also play a role in regulating DeltaFosB's transcriptional activity.

The transcription factor DeltaFosB is recruited by inflammatory pain.

DeltaFosB, a stable splice variant of FosB, has been proposed to mediate persistent brain adaptation in response to several chronic perturbations, but it has not yet been considered in the context of sustained pain. Inflammatory pain induces neuronal plasticity that can result in persistent alteration of nociceptive pathways. This neuronal plasticity can partly result from changes in gene expression controlled by transcription factors.

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.

DeltaFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment.

The transcription factor deltaFosB is induced in the nucleus accumbens and dorsal striatum by chronic exposure to several drugs of abuse, and increasing evidence supports the possibility that this induction is involved in the addiction process. However, to date there has been no report of deltaFosB induction by drugs of abuse in the ventral tegmental area (VTA), which is also a critical brain reward region. In the present study, we used immunohistochemistry to demonstrate that chronic forced administration of cocaine induces deltaFosB in the rat VTA.

DeltaFosB: a molecular switch for long-term adaptation in the brain.

DeltaFosB is a unique transcription factor that plays an essential role in long-term adaptive changes in the brain associated with diverse conditions, such as drug addiction, Parkinson's disease, depression, and antidepressant treatment. It is induced in brain, in a region- and cell-type-specific manner by many types of chronic perturbations. Once induced, it persists for long periods of time due to its unusual stability.

Induction of deltaFosB in reward-related brain structures after chronic stress.

Acute and chronic stress differentially regulate immediate-early gene (IEG) expression in the brain. Although acute stress induces c-Fos and FosB, repeated exposure to stress desensitizes the c-Fos response, but FosB-like immunoreactivity remains high. Several other treatments differentially regulate IEG expression in a similar manner after acute versus chronic exposure.

Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP). Evidence for integrated co-receptor function betwenn LRP and the PDGF.

The low density lipoprotein receptor-related protein (LRP) functions in the catabolism of numerous ligands including proteinases, proteinase inhibitor complexes, and lipoproteins. In the current study we provide evidence indicating an expanded role for LRP in modulating cellular signaling events. Our results show that platelet-derived growth factor (PDGF) BB induces a transient tyrosine phosphorylation of the LRP cytoplasmic domain in a process dependent on PDGF receptor activation and c-Src family kinase activity.