fosB

fosB(FBJ murine osteosarcoma viral oncogene homolog B 또는 FosB) 및 G0/G1 스위치 조절 단백질 3(G0S3,G0/G1 switch regulatory protein 3)로도 알려진 단백질 fosB는 인간에서 FBJ 뮤린 골육종 바이러스 종양 유전자 상동체 B(FOSB) 유전자(gene)에 의해 인코딩되는 단백질로 알려져있다.^[1]^[2]^[3]

작용[편집 | 원본 편집]

다른 많은 유전자가 그러하듯이 어떤 특정 유전자는 독립적으로 발현하여 기능을 행사하기보다는 다른 유전자의 발현으로 작동하는 기능들과 직간접적으로 연동된다는 점을 전제로 fosB 역시 파킨슨병같은 운동 이상증이나 보상과 관련한 감수성을 향상하는 복잡한 양육행동과 관련있다고 연구보고된바있다. 또다른 연구결과에서는 JunD유전자 발현과 관련해서 이와는 상반된 과정에서 FosB는 중독에서 가장 중요한 생체 분자 기전으로 언급된바 있다. ^[4]^[5]^[6]^[7]^[8]

각주

↑ Entrez Gene: FOSB FBJ murine osteosarcoma viral oncogene homolog B.
↑ (1990년 10월 1일) A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes. 《DNA and Cell Biology》 9 (8): 579–87. PMID 1702972. doi 10.1089/dna.1990.9.579doi 10.1089/dna.1990.9.579.
↑ (1992년 4월 1일) Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3. 《Nature Genetics》 1 (1): 34–9. PMID 1301997. doi 10.1038/ng0492-34doi 10.1038/ng0492-34.
↑ [참고]Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews. Neuroscience. 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."
↑ [참고]Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology. 61 (7): 1109–22. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101. "Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)." Table 1
↑ [참고]Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. "Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict."
↑ Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". Journal of Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964.
↑ [참고]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. S2CID 23904956.

[entrez-1] Entrez Gene: FOSB FBJ murine osteosarcoma viral oncogene homolog B.

[pmid1702972-2] (1990년 10월 1일) A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes. 《DNA and Cell Biology》 9 (8): 579–87. PMID 1702972. doi 10.1089/dna.1990.9.579doi 10.1089/dna.1990.9.579.

[pmid1301997-3] (1992년 4월 1일) Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3. 《Nature Genetics》 1 (1): 34–9. PMID 1301997. doi 10.1038/ng0492-34doi 10.1038/ng0492-34.

[4] [참고]Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews. Neuroscience. 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."

[5] [참고]Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology. 61 (7): 1109–22. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101. "Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)." Table 1

[6] [참고]Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. "Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict."

[7] Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". Journal of Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964.

[8] [참고]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. S2CID 23904956.

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