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FOSB

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Template:PBB FBJ murine osteosarcoma viral oncogene homolog B also known as FOSB (in humans) or FosB (in other species) is a protein that, in humans, is encoded by the FOSB gene.[1][2][3]

The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation.[1]

Delta FosB

Delta FosB is a truncated splice variant of FosB.[4] Delta FosB has been implicated in the development of drug addiction and control of the reward system in the brain, and is linked to changes in a number of other gene products such as CREB and sirtuins.[5][6][7][8][9][10] Delta FosB also regulates the commitment of mesenchymal precursor cells to the adipocyte or osteoblast lineage.[11]

Role in cocaine use

Delta FosB levels have been found to increase upon the use of cocaine.[12] Each subsequent dose of cocaine will continue to increase the levels of Delta FosB with no ceiling of tolerance. Increasing the levels of Delta FosB has led to increases in brain-derived neurotrophic factor (BDNF) levels, which in turn will increase the number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug. This consequence of cocaine use may attribute to the idea of sensitization presented with the drug.

Transgenic mice exhibiting inducible expression of delta FosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to drugs.[13] They self-administer cocaine at lower doses than control,[14] but have a greater likelihood of relapse when the drug is withheld.[14][15] Delta FosB increases the expression of AMPA receptor subunit GluR2[13] and also decreases expression of dynorphin, thereby enhancing the sensitivity to reward.[15]

See also

References

  1. ^ a b "Entrez Gene: FOSB FBJ murine osteosarcoma viral oncogene homolog B".
  2. ^ Siderovski DP, Blum S, Forsdyke RE, Forsdyke DR (October 1990). "A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes". DNA Cell Biol. 9 (8): 579–87. doi:10.1089/dna.1990.9.579. PMID 1702972.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Martin-Gallardo A, McCombie WR, Gocayne JD, FitzGerald MG, Wallace S, Lee BM, Lamerdin J, Trapp S, Kelley JM, Liu LI (April 1992). "Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3". Nat. Genet. 1 (1): 34–9. doi:10.1038/ng0492-34. PMID 1301997.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Nakabeppu Y, Nathans D (February 1991). "A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity". Cell. 64 (4): 751–9. doi:10.1016/0092-8674(91)90504-R. PMID 1900040.
  5. ^ Werme M, Messer C, Olson L; et al. (2002). "Delta FosB regulates wheel running". J. Neurosci. 22 (18): 8133–8. PMID 12223567. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  6. ^ McClung CA, Nestler EJ (November 2003). "Regulation of gene expression and cocaine reward by CREB and DeltaFosB". Nature Neuroscience. 6 (11): 1208–15. doi:10.1038/nn1143. PMID 14566342.
  7. ^ Nestler EJ (October 2008). "Review. Transcriptional mechanisms of addiction: role of DeltaFosB". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 363 (1507): 3245–55. doi:10.1098/rstb.2008.0067. PMC 2607320. PMID 18640924.
  8. ^ Renthal W, Carle TL, Maze I, Covington HE, Truong HT, Alibhai I, Kumar A, Montgomery RL, Olson EN, Nestler EJ (July 2008). "Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure". Journal of Neuroscience. 28 (29): 7344–9. doi:10.1523/JNEUROSCI.1043-08.2008. PMC 2610249. PMID 18632938.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Renthal W, Nestler EJ (August 2008). "Epigenetic mechanisms in drug addiction". Trends in Molecular Medicine. 14 (8): 341–50. doi:10.1016/j.molmed.2008.06.004. PMC 2753378. PMID 18635399.
  10. ^ Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ (May 2009). "Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins". Neuron. 62 (3): 335–48. doi:10.1016/j.neuron.2009.03.026. PMC 2779727. PMID 19447090.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Sabatakos G, Sims NA, Chen J, Aoki K, Kelz MB, Amling M, Bouali Y, Mukhopadhyay K, Ford K, Nestler EJ, Baron R (September 2000). "Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis". Nature Medicine. 6 (9): 985–90. doi:10.1038/79683. PMID 10973317.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Hope BT (May 1998). "Cocaine and the AP-1 transcription factor complex". Ann. N. Y. Acad. Sci. 844: 1–6. doi:10.1111/j.1749-6632.1998.tb08216.x. PMID 9668659.
  13. ^ a b Kelz MB, Chen J, Carlezon WA, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ (September 1999). "Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine". Nature. 401 (6750): 272–6. doi:10.1038/45790. PMID 10499584.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ a b Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW (March 2003). "Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine". J. Neurosci. 23 (6): 2488–93. PMID 12657709.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ a b Nestler EJ, Barrot M, Self DW (September 2001). "DeltaFosB: a sustained molecular switch for addiction". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11042–6. doi:10.1073/pnas.191352698. PMC 58680. PMID 11572966.{{cite journal}}: CS1 maint: multiple names: authors list (link)

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


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