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.
The dominant negative mutant variant of JunD, known as ΔJunD or Delta JunD, is a potent antagonist of the ΔFosB transcript, as well as other forms of AP-1-mediated transcriptional activity. In the nucleus accumbens, ΔJunD directly opposes many of the neurological changes that occur in addiction, i.e., those induced by ΔFosB. ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders.
^ abRobison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci.12 (11): 623–37. doi:10.1038/nrn3111. PMC3272277. PMID21989194. 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.
^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 384–385. ISBN9780071481274.
Trask B, Fertitta A, Christensen M, Youngblom J, Bergmann A, Copeland A, de Jong P, Mohrenweiser H, Olsen A, Carrano A (1993). "Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers". Genomics15 (1): 133–45. doi:10.1006/geno.1993.1021. PMID8432525.
Dorsey MJ, Tae HJ, Sollenberger KG, Mascarenhas NT, Johansen LM, Taparowsky EJ (1995). "B-ATF: a novel human bZIP protein that associates with members of the AP-1 transcription factor family". Oncogene11 (11): 2255–65. PMID8570175.
Claret FX, Hibi M, Dhut S, Toda T, Karin M (1996). "A new group of conserved coactivators that increase the specificity of AP-1 transcription factors". Nature383 (6599): 453–7. doi:10.1038/383453a0. PMID8837781.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Labudova O, Krapfenbauer K, Moenkemann H, Rink H, Kitzmüller E, Cairns N, Lubec G (1998). "Decreased transcription factor junD in brains of patients with Down syndrome". Neurosci. Lett.252 (3): 159–62. doi:10.1016/S0304-3940(98)00569-2. PMID9739985.
Venugopal R, Jaiswal AK (1998). "Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes". Oncogene17 (24): 3145–56. doi:10.1038/sj.onc.1202237. PMID9872330.
Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL (1999). "Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription". Cell96 (1): 143–52. doi:10.1016/S0092-8674(00)80967-8. PMID9989505.
Miyamoto NG, Medberry PS, Hesselgesser J, Boehlk S, Nelson PJ, Krensky AM, Perez HD (2000). "Interleukin-1beta induction of the chemokine RANTES promoter in the human astrocytoma line CH235 requires both constitutive and inducible transcription factors". J. Neuroimmunol.105 (1): 78–90. doi:10.1016/S0165-5728(00)00195-8. PMID10713367.
Sharma SC, Richards JS (2000). "Regulation of AP1 (Jun/Fos) factor expression and activation in ovarian granulosa cells. Relation of JunD and Fra2 to terminal differentiation". J. Biol. Chem.275 (43): 33718–28. doi:10.1074/jbc.M003555200. PMID10934195.