JunD

For the military districts under the early Caliphates, see Jund.
Jun D proto-oncogene
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols JUND ; AP-1
External IDs OMIM: 165162 MGI: 96648 HomoloGene: 3910 GeneCards: JUND Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 3727 16478
Ensembl ENSG00000130522 ENSMUSG00000071076
UniProt P17535 P15066
RefSeq (mRNA) NM_001286968 NM_001286944
RefSeq (protein) NP_001273897 NP_001273873
Location (UCSC) Chr 19:
18.28 – 18.28 Mb
Chr 8:
70.7 – 70.7 Mb
PubMed search

Transcription factor JunD is a protein that in humans is encoded by the JUND gene.[1][2]

Function

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.[3]

ΔJunD

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.[4][5][6] In the nucleus accumbens, ΔJunD directly opposes many of the neurological changes that occur in addiction, i.e., those induced by ΔFosB.[5][6] ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders[7] (e.g., those which induce expression of ΔJunD in the nucleus accumbens).

Interactions

JunD has been shown to interact with ATF3,[8] MEN1,[9] DNA damage-inducible transcript 3[10] and BRCA1.[11]

See also

References

  1. Nomura N, Ide M, Sasamoto S, Matsui M, Date T, Ishizaki R (July 1990). "Isolation of human cDNA clones of jun-related genes, jun-B and jun-D". Nucleic Acids Res. 18 (10): 3047–8. doi:10.1093/nar/18.10.3047. PMC 330838. PMID 2112242.
  2. Berger I, Shaul Y (June 1991). "Structure and function of human jun-D". Oncogene 6 (4): 561–6. PMID 1903194.
  3. "Entrez Gene: JUND jun D proto-oncogene".
  4. Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–98. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.
  5. 1 2 Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. 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.
  6. 1 2 Pitchers KK, Frohmader KS, Vialou V, Mouzon E, Nestler EJ, Lehman MN, Coolen LM (October 2010). "ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward". Genes Brain Behav. 9 (7): 831–40. doi:10.1111/j.1601-183X.2010.00621.x. PMC 2970635. PMID 20618447.
  7. 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. ISBN 9780071481274.
  8. Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (January 1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Mol. Endocrinol. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.
  9. Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL (January 1999). "Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription". Cell 96 (1): 143–52. doi:10.1016/S0092-8674(00)80967-8. PMID 9989505.
  10. Ubeda M, Vallejo M, Habener JF (November 1999). "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Mol. Cell. Biol. 19 (11): 7589–99. PMC 84780. PMID 10523647.
  11. Hu YF, Li R (June 2002). "JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction". Genes Dev. 16 (12): 1509–17. doi:10.1101/gad.995502. PMC 186344. PMID 12080089.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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