Transcription factor JunD is a protein that in humans is encoded by the JUND gene.[5][6]
The protein encoded by this intronless gene is a member of the JUN family, and a functional component of the AP1 transcription factor complex. It has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternate translation initiation site usage results in the production of different isoforms.[7]
The dominant negative mutant variant of JunD, known as ΔJunDorDelta JunD, is a potent antagonist of the ΔFosB transcript, as well as other forms of AP-1-mediated transcriptional activity.[8][9][10] In the nucleus accumbens, ΔJunD directly opposes many of the neurological changes that occur in addiction (i.e., those induced by ΔFosB).[9][10] ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders.[11] Being an unnatural genetic variant, deltaJunD has not been observed in humans.
JunD has been shown to interact with ATF3,[12] MEN1,[13] DNA damage-inducible transcript 3[14] and BRCA1.[15]
ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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