JunD explained

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). ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders.^[7] Being an unnatural genetic variant, deltaJunD has not been observed in humans.

Interactions

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

See also

• AP-1 (transcription factor)

Further reading

• Mollinedo F, Vaquerizo MJ, Naranjo JR . Expression of c-jun, jun B and jun D proto-oncogenes in human peripheral-blood granulocytes . Biochem. J. . 273(Pt 2) . 2. 477–9 . 1991 . 1899335 . 1149869 . 10.1042/bj2730477.
• Franklin CC, McCulloch AV, Kraft AS . In vitro association between the Jun protein family and the general transcription factors, TBP and TFIIB . Biochem. J. . 305 . 3 . 967–74 . 1995 . 7848298 . 1136352 . 10.1042/bj3050967.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ . Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression . Mol. Endocrinol. . 8 . 1 . 59–68 . 1994 . 8152431 . 10.1210/mend.8.1.8152431 . free .
• Trask B, Fertitta A, Christensen M, Youngblom J, Bergmann A, Copeland A, de Jong P, Mohrenweiser H, Olsen A, Carrano A . Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers . Genomics . 15 . 1 . 133–45 . 1993 . 8432525 . 10.1006/geno.1993.1021 .
• Dorsey MJ, Tae HJ, Sollenberger KG, Mascarenhas NT, Johansen LM, Taparowsky EJ . B-ATF: a novel human bZIP protein that associates with members of the AP-1 transcription factor family . Oncogene . 11 . 11 . 2255–65 . 1995 . 8570175 .
• Claret FX, Hibi M, Dhut S, Toda T, Karin M . A new group of conserved coactivators that increase the specificity of AP-1 transcription factors . Nature . 383 . 6599 . 453–7 . 1996 . 8837781 . 10.1038/383453a0 . 1996Natur.383..453C . 4353893 .
• Kallunki T, Deng T, Hibi M, Karin M . c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions . Cell . 87 . 5 . 929–39 . 1996 . 8945519 . 10.1016/S0092-8674(00)81999-6 . 10345690 . free .
• Aronheim A, Zandi E, Hennemann H, Elledge SJ, Karin M . Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions . Mol. Cell. Biol. . 17 . 6 . 3094–102 . 1997 . 9154808 . 232162 . 10.1128/mcb.17.6.3094.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Labudova O, Krapfenbauer K, Moenkemann H, Rink H, Kitzmüller E, Cairns N, Lubec G . Decreased transcription factor junD in brains of patients with Down syndrome . Neurosci. Lett. . 252 . 3 . 159–62 . 1998 . 9739985 . 10.1016/S0304-3940(98)00569-2 . 44836385 .
• Venugopal R, Jaiswal AK . Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes . Oncogene . 17 . 24 . 3145–56 . 1998 . 9872330 . 10.1038/sj.onc.1202237 . 7917564 .
• Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL . Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription . Cell . 96 . 1 . 143–52 . 1999 . 9989505 . 10.1016/S0092-8674(00)80967-8 . 18116746 . free .
• Liberati NT, Datto MB, Frederick JP, Shen X, Wong C, Rougier-Chapman EM, Wang XF . Smads bind directly to the Jun family of AP-1 transcription factors . Proc. Natl. Acad. Sci. U.S.A. . 96 . 9 . 4844–9 . 1999 . 10220381 . 21779 . 10.1073/pnas.96.9.4844 . 1999PNAS...96.4844L . free .
• Gobl AE, Berg M, Lopez-Egido JR, Oberg K, Skogseid B, Westin G . Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism . Biochim. Biophys. Acta . 1447 . 1 . 51–6 . 1999 . 10500243 . 10.1016/S0167-4781(99)00132-3 .
• Ubeda M, Vallejo M, Habener JF . CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins . Mol. Cell. Biol. . 19 . 11 . 7589–99 . 1999 . 10523647 . 84780 . 10.1128/MCB.19.11.7589.
• Miyamoto NG, Medberry PS, Hesselgesser J, Boehlk S, Nelson PJ, Krensky AM, Perez HD . 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 . 2000 . 10713367 . 10.1016/S0165-5728(00)00195-8 . 8547340 .
• Sharma SC, Richards JS . 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 . 2000 . 10934195 . 10.1074/jbc.M003555200 . free .

External links

• • • PDBe-KB provides an overview of all the structure information available in the PDB for Human Transcription factor jun-D

Notes and References

1. Nomura N, Ide M, Sasamoto S, Matsui M, Date T, Ishizaki R . Isolation of human cDNA clones of jun-related genes, jun-B and jun-D . Nucleic Acids Res. . 18 . 10 . 3047–8 . July 1990 . 2112242 . 330838 . 10.1093/nar/18.10.3047 .
2. Berger I, Shaul Y . Structure and function of human jun-D . Oncogene . 6 . 4 . 561–6 . June 1991 . 1903194 .
3. Web site: Entrez Gene: JUND jun D proto-oncogene.
4. Hyman SE, Malenka RC, Nestler EJ . Neural mechanisms of addiction: the role of reward-related learning and memory . Annu. Rev. Neurosci. . 29 . 565–98 . 2006 . 16776597 . 10.1146/annurev.neuro.29.051605.113009 .
5. Robison AJ, Nestler EJ . Transcriptional and epigenetic mechanisms of addiction . Nat. Rev. Neurosci. . 12 . 11 . 623–37 . November 2011 . 21989194 . 3272277 . 10.1038/nrn3111 . 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. Pitchers KK, Frohmader KS, Vialou V, Mouzon E, Nestler EJ, Lehman MN, Coolen LM . ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward . Genes Brain Behav. . 9 . 7 . 831–40 . October 2010 . 20618447 . 2970635 . 10.1111/j.1601-183X.2010.00621.x .
7. Book: Malenka RC, Nestler EJ, Hyman SE . Sydor A, Brown RY . Molecular Neuropharmacology: A Foundation for Clinical Neuroscience . 2009 . McGraw-Hill Medical . New York . 9780071481274 . 384–385 . 2nd . Chapter 15: Reinforcement and addictive disorders .
8. Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ . Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression . Mol. Endocrinol. . 8 . 1 . 59–68 . January 1994 . 8152431 . 10.1210/mend.8.1.8152431 . free .
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 . Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription . Cell . 96 . 1 . 143–52 . January 1999 . 9989505 . 10.1016/S0092-8674(00)80967-8 . 18116746 . free .
10. Ubeda M, Vallejo M, Habener JF . CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins . Mol. Cell. Biol. . 19 . 11 . 7589–99 . November 1999 . 10523647 . 84780 . 10.1128/MCB.19.11.7589 .
11. Hu YF, Li R . JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction . Genes Dev. . 16 . 12 . 1509–17 . June 2002 . 12080089 . 186344 . 10.1101/gad.995502 .