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組織蛋白酶B

本頁使用了標題或全文手工轉換
維基百科，自由的百科全書
組織蛋白酶B
已知的結構
PDB直系同源搜尋: PDBe RCSB
識別號
別名CTSB；, APPS, CPSB, cathepsin B, RECEUP
外部IDOMIM：116810 MGI：88561 HomoloGene：37550 GeneCards：CTSB
基因位置（人類）
8號染色體
染色體8號染色體[1]
8號染色體
組織蛋白酶B的基因位置
組織蛋白酶B的基因位置
基因座8p23.1起始11,842,524 bp[1]
終止11,869,448 bp[1]
RNA表達模式




查閱更多表達數據
直系同源
物種人類小鼠
Entrez

1508

13030

Ensembl

ENSG00000164733
​ENSG00000285132

ENSMUSG00000021939

UniProt

P07858

P10605

mRNA​序列

NM_007798

蛋白序列

NP_031824

基因位置​（UCSC）Chr 8: 11.84 – 11.87 MbChr 14: 63.36 – 63.38 Mb
PubMed​查找[3][4]
維基數據
檢視/編輯人類檢視/編輯小鼠

組織蛋白酶B（英文：Cathepsin B）屬於溶酶體半胱氨酸蛋白酶家族，也叫半胱氨酸組織蛋白酶，在細胞內蛋白水解中起重要作用。[5]在人體內的組織蛋白酶B被編碼為CTSB基因。[6][7]組織蛋白酶B的水平在某些癌症、癌前病變和各種其他病理狀況中會上調。[8][9][10][11]

結構

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基因

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CTSB基因位於染色體8p22，由13個外顯子組成。CTSB基因位於8p22染色體，由13個外顯子組成。CTSB基因的啟動子含有一個富含GC的區域，包含許多SP1位點，類似於管家基因。[12]已發現該基因至少有五個編碼相同蛋白質的轉錄變體。[13]

蛋白質

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組織蛋白酶B在粗糙內質網上合成為339個氨基酸的前酶原，具有17個氨基酸的信號肽。[14][15]然後將43/46 kDa的組織蛋白酶原B轉運到高爾基體，在那裏將形成組織蛋白酶B。成熟的組織蛋白酶B由25-26 kDa的重鏈和5 kDa的輕鏈組成，它們通過二硫鍵的二聚體連接。

功能

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組織蛋白酶B可增強其他蛋白酶的活性，包括基質金屬蛋白酶、尿激酶（絲氨酸蛋白酶尿激酶纖溶酶原活化劑）和組織蛋白酶D。[16][17]因此，它在細胞外基質成分的蛋白水解、細胞間通訊中斷和減少蛋白酶抑制劑的表達方面具有重要作用。[18]它還參與自噬和分解代謝，有造成腫瘤的惡性發展，並可能參與特異性免疫抵抗。[19]此外，它被確定為具有較小的連接酶活性，能夠通過酰胺鍵連接肽片段。[20]

臨床意義

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組織蛋白酶B可以作為多種癌症的潛在有效生物標誌物。.[16][21][22][23][24][25] 組織蛋白酶B的過度表達與侵襲性和轉移性癌症有關。[26]組織蛋白酶B在新陳代謝過程中在肌肉組織中產生。它能夠穿過血腦屏障[27]並且與神經發生有關，特別是在小鼠齒狀回中。多種疾病導致組織蛋白酶B水平升高，從而導致許多病理過程，包括細胞死亡、炎症和有毒肽的產生。專注於神經系統疾病，在癲癇齧齒動物模型中的組織蛋白酶 B 基因敲除研究表明，組織蛋白酶B會導致大量因誘發癲癇而發生的凋亡細胞死亡。[28]

對誘發癲癇發作的老鼠進行組織蛋白酶B抑制劑治療，可改善神經系統評分、學習能力，並大大減少神經元細胞死亡和促凋亡細胞死亡肽。[29]同樣，在創傷性腦損傷老鼠模型中組織蛋白酶B基因敲除和組織蛋白酶B抑制劑治療研究表明，組織蛋白酶B是導致神經肌肉功能障礙、記憶喪失、神經元細胞死亡以及增加促壞死與促凋亡細胞死亡肽的關鍵。[30][31]在缺血性非人類靈長類動物和齧齒動物模型中，組織蛋白酶B抑制劑治療可防止腦神經元顯着喪失，尤其是在海馬體中的神經元。[32][33][34]在肺炎鏈球菌腦膜炎齧齒動物模型中，組織蛋白酶B抑制劑治療極大地改善了感染的臨床過程，並減少了腦部炎症和炎症性白血球介素-1β （IL1-β）和腫瘤壞死因子-α（TNF-α）。[35]

在表達人類前類澱粉蛋白質（APP）的轉基因阿爾茨海默症動物模型中，該模型含有在大多數阿爾茨海默症患者或豚鼠中發現的野生型β-分泌酶位點序列，這是人類野生型APP加工的自然模型, 遺傳上刪除組織蛋白酶B基因或化學上抑制組織蛋白酶B大腦活動導致此類小鼠的記憶缺陷得到顯着改善並降低神經毒性全長β澱粉樣蛋白(1-40/42)和特別有害的焦穀氨酸β澱粉樣蛋白的水平(3-40/42)，這被認為是導致疾病的原因。[36][37][38][39][40][41][42]在一個非轉基的因衰老加速的小鼠品系中，它也具有含有野生型β-分泌酶位點序列的APP，用銀杏葉提取出的白果內酯，也可以通過組織蛋白酶B抑制劑降低了β澱粉樣蛋白。[43]此外，siRNA 沉默或化學抑制具有人類野生型 β-分泌酶活性的原代齧齒動物海馬細胞或牛嗜鉻細胞中的組織蛋白酶B，可通過調節分泌途徑減少β澱粉樣蛋白的分泌。[44][45]CTSB基因的突變與熱帶胰腺炎（一種慢性胰腺炎）有關。[46]

相互作用

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組織蛋白酶B可以與以下物質產生相互作用：

組織蛋白酶B可以被以下物質抑制：

參見

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參考文獻

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