FOSB
位於19號人類染色體的基因
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FBJ murine osteosarcoma viral oncogene homolog B,又名為FOSB 或 FosB，是一個在人體中由FOSB 基因編碼（encoded）的蛋白質。 [參1][參2][參3]FOS 基因家族由四個成員組成：FOS、 FOSB、 FOSL1、和FOSL2。 這些基因組成（encode） 亮氨酸拉鏈（leucine zipper）蛋白質。這種蛋白質可以與JUN 這個蛋白質及其家族 (e.g., c-Jun、JunD) 二聚體化（dimerize），然後形成轉錄因子（transcription factor）綜合區－AP-1轉錄因子[註1]。
如同這些，FOS蛋白質就被表示成關於細胞增加、細胞差異化、細胞轉型的調節者。 [註2][參1]
FosB與其選擇性剪接形成的產物——「ΔFosB」和進一步剪接而成的「'Δ2ΔFosB」都參與到了骨硬化的過程之中，但 Δ2ΔFosB 沒有已知的轉錄活化區域，無法通過AP-1 複合物影響轉錄過程。[參4]
現已知ΔFosB之端點銜接處的變化程度是發展並維持病理行為和神經可塑性的核心因素（充分且必要因素）。而病理行為和神經可塑性都參與了行為成癮（與自然酬賞相關）及藥物成癮的形成過程。[參5]
註解
編輯- ^ 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.
參考資料
編輯- ^ 1.0 1.1 Entrez Gene: FOSB FBJ murine osteosarcoma viral oncogene homolog B. （原始內容存檔於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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