FOSB
位於19號人類染色體的基因
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FBJ murine osteosarcoma viral oncogene homolog B,又名为FOSB 或 FosB，是一个在人体中由FOSB 基因编码（encoded）的蛋白质。 [参1][参2][参3]FOS 基因家族由四个成员组成：FOS、 FOSB、 FOSL1、和FOSL2。 这些基因组成（encode） 亮氨酸拉链（leucine zipper）蛋白质。这种蛋白质可以与JUN 这个蛋白质及其家族 (e.g., c-Jun、JunD) 二聚体化（dimerize），然后形成转录因子（transcription factor）综合区－AP-1转录因子[注1]。
如同这些，FOS蛋白质就被表示成关于细胞增加、细胞差异化、细胞转型的调节者。 [注2][参1]
FosB与其选择性剪接形成的产物——“ΔFosB”和进一步剪接而成的“'Δ2ΔFosB”都参与到了骨硬化的过程之中，但 Δ2ΔFosB 没有已知的转录激活区域，无法通过AP-1 复合物影响转录过程。[参4]
现已知ΔFosB之端点衔接处的变化程度是发展并维持病理行为和神经可塑性的核心因素（充分且必要因素）。而病理行为和神经可塑性都参与了行为成瘾（与自然酬赏相关）及药物成瘾的形成过程。[参5]
注解
- ^ 原文：hese genes encode leucine zipper proteins that can dimerize with proteins of the JUN family (e.g., c-Jun, JunD), thereby forming the transcription factor complex AP-1.
- ^ 原文：As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation.
参考资料
- ^ 1.0 1.1 Entrez Gene: FOSB FBJ murine osteosarcoma viral oncogene homolog B. （原始内容存档于2019-10-16）.
- ^ Siderovski DP, Blum S, Forsdyke RE, Forsdyke DR. 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. Oct 1990, 9 (8): 579–87. PMID 1702972. doi:10.1089/dna.1990.9.579.
- ^ Martin-Gallardo A, McCombie WR, Gocayne JD, FitzGerald MG, Wallace S, Lee BM, Lamerdin J, Trapp S, Kelley JM, Liu LI. Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3. Nature Genetics. Apr 1992, 1 (1): 34–9. PMID 1301997. doi:10.1038/ng0492-34.
- ^ Sabatakos G, Rowe GC, Kveiborg M, Wu M, Neff L, Chiusaroli R, Philbrick WM, Baron R. Doubly truncated FosB isoform (Delta2DeltaFosB) induces osteosclerosis in transgenic mice and modulates expression and phosphorylation of Smads in osteoblasts independent of intrinsic AP-1 activity. Journal of Bone and Mineral Research. 2008-05, 23 (5): 584–95. PMC 2674536
. PMID 18433296. doi:10.1359/jbmr.080110.
- ^ Ruffle JK. Molecular neurobiology of addiction: what's all the (Δ)FosB about?. The American Journal of Drug and Alcohol Abuse. Nov 2014, 40 (6): 428–37. PMID 25083822. doi:10.3109/00952990.2014.933840.
ΔFosB as a therapeutic biomarker
The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. If ΔFosB detection is indicative of chronic drug exposure (and is at least partly responsible for dependence of the substance), then its monitoring for therapeutic efficacy in interventional studies is a suitable biomarker (Figure 2). Examples of therapeutic avenues are discussed herein. ...
Conclusions
ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a ‘‘molecular switch’’ (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
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