FOSB

FOSB
識別號
別名	FOSB；, AP-1, G0S3, GOS3, GOSB, FosB, ΔFosB, FosB proto-oncogene, AP-1 transcription factor subunit
外部ID	OMIM：164772 MGI：95575 HomoloGene：31403 GeneCards：FOSB
基因位置（人類）
染色體	19號染色體
終止	45,475,179 bp
基因位置（小鼠）
染色體	小鼠7號染色體
終止	19,043,976 bp
RNA表現模式
	查閱更多表現資料
基因本體
分子功能	• DNA結合; • sequence-specific DNA binding; • DNA結合轉錄因子活性; • DNA-binding transcription activator activity, RNA polymerase II-specific; • 轉錄因子結合; • double-stranded DNA binding; • RNA polymerase II cis-regulatory region sequence-specific DNA binding; • DNA-binding transcription factor activity, RNA polymerase II-specific;
細胞組分	• 細胞內膜結合胞器; • 細胞核; • 核質;
生物學過程	• cellular response to calcium ion; • regulation of transcription, DNA-templated; • regulation of transcription by RNA polymerase II; • response to progesterone; • female pregnancy; • response to corticosterone; • response to mechanical stimulus; • negative regulation of transcription by RNA polymerase II; • transcription by RNA polymerase II; • response to morphine; • cellular response to hormone stimulus; • response to cAMP; • positive regulation of transcription by RNA polymerase II;
	Sources:Amigo / QuickGO
直系同源
	2354
	14282
	ENSG00000125740
	ENSMUSG00000003545
	P53539
	P13346
	NM_001114171; NM_006732
	NM_008036; NM_001347586
	NP_001107643; NP_006723
	NP_001334515; NP_032062
	維基資料
檢視/編輯人類	檢視/編輯小鼠

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（英語：C-Fos）、 FOSB、 FOSL1（英語：FOSL1）、和FOSL2（英語：FOSL2）。這些基因組成（encode）白胺酸拉鏈（leucine zipper）蛋白質。這種蛋白質可以與JUN（英語：C-jun）這個蛋白質及其家族 (e.g., c-Jun（英語：c-Jun）、JunD（英語：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（英語：osteosclerosis）的過程之中，但 Δ2ΔFosB 沒有已知的轉錄活化區域（英語：transactivation domain），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（英語：splice）的變化程度（英語：Variant_of_uncertain_significance）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（英語：natural reward）相關）及藥物成癮的形成過程。^[參5]

註解

註:

^ 原文：hese genes encode leucine zipper proteins that can dimerize with proteins of the JUN（英語：C-jun） family (e.g., c-Jun（英語：c-Jun）, JunD（英語：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

參:

^ ^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.

外部連結

ROLE OF ΔFOSB IN THE NUCLEUS ACCUMBENS（頁面存檔備份，存於網際網路檔案館）
KEGG Pathway – human alcohol addiction（頁面存檔備份，存於網際網路檔案館）
KEGG Pathway – human amphetamine addiction（頁面存檔備份，存於網際網路檔案館）
KEGG Pathway – human cocaine addiction（頁面存檔備份，存於網際網路檔案館）

註解

參考資料

外部連結

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