摘要:高遷移率族核小體結合蛋白(High-mobility group nucleosome-binding proteins,HMGN)幾乎存在于所有哺乳動物和多數脊椎動物的細胞核中,屬于HMG蛋白家族。HMGN是現在唯一已知的特異性結合在核小體上的非組蛋白,能夠改變染色質的結構、增強染色質模板的轉錄/復制,參與DNA復制/表達、細胞分化、器官發育及基因表達調控等細胞的生命活動。目前,HMGN包括HMGN1、HMGN2、HMGN3、HMGN4和HMGN5。研究顯示,HMGN1據其所在位置的不同,有著截然不同的功能。在細胞核內,HMGN1作為一種特殊定位的生物蛋白,與核小體直接結合而調節基因的轉錄和影響染色質的結構;在細胞外環境,HMGN1通過toll樣受體4(Toll-like receptor 4,TLR4)促進抗原提呈細胞(Antigen-presenting cells,APCs)的活化和補充,從而促進特定抗原免疫應答。警報素(Alarmins)是一種內源性介質,當機體受到危險信號刺激時,它能快速的釋放到細胞外,招募并激活APCs增強特異性免疫和非特異性免疫反應。認識HMGN及其作用對其在多方面的應用有重要意義。
關鍵詞:高遷移率族核小體蛋白(HMGN);警報素;核小體;免疫
中圖分類號:R39211
文獻標識碼:A
文章編號:1008-0457(2017)03-0068-07國際DOI編碼:10.15958/j.cnki.sdnyswxb.2017.03.012
Abstract:High-mobility group nucleosome-binding proteins are members of the high mobility group protein familyHMGN exists in the nucleus of the almost all mammals and most vertebratesHMGN are the only non-histone proteins known to specifically bind inside the nucleosomes,which can change chromatin structure,enhance transcription and replication of chromatin template,and participate in DNA replication and expression,cell differentiation,organ development and gene expression regulation and other cell life activitiesHMGN protein family is composed of five proteins,HMGN1 through 5Previous studies indicated that HMGN1 has two distinct functions depending on its positionIn nucleus,HMGN1 acts as a location-specific biological protein,and can regulate gene transcription and influence chromatin structure by directly binding to nucleosomesHo-wever,extracellular HMGN1 promotes antigen-specific immune responses by promoting the activation and recruitment of antigen-presenting cells(APCs)through toll-like receptor 4(TLR4)Alarmins,as endogenous mediators,could be rapidly released from cells in response to dangerous signalsAlarmin then recruits and activates APCs to enhance innate and adaptive immune responsesHMGN1 is a recently identified alarminHere,we introduce the HMGN and its potential role in medical and other possible fields
Key words:highmobility group nucleosome-binding protein 1(HMGN1);alarmins;nucleosome;immunity
HMG蛋白的首次發現是在1973年,Johns EW與同事Goodwin GH和Sanders C從小牛胸腺細胞中通過035-M-NaCl提取分離得到兩組蛋白質[1,2],一組蛋白易溶于10%的三氯乙酸,因在聚丙烯酰胺凝膠電泳中遷移快速,將其稱為“高遷移率族”蛋白,即HMG蛋白;另一組蛋白質在聚丙烯酰胺凝膠電泳中遷移較慢,將其稱為“低遷移率族”蛋白[1]。隨后,實驗通過凝膠過濾部分分離HMG蛋白發現,HMG蛋白中至少含有兩種蛋白,命名為蛋白1(HMG-1)和蛋白2(HMG-2),這兩種蛋白質的酸/堿性氨基酸都超過55%,每個細胞核中約105分子的HMG-1和2[1,2]。……