活化誘導性胞苷去胺酶
![本頁使用了標題或全文手工轉換](http://upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Zh_conversion_icon_m.svg/35px-Zh_conversion_icon_m.svg.png)
活化誘導性胞苷去胺酶(Activation-induced cytidine deaminase,簡稱AID)是一種胞苷去胺酶,屬APOBEC去胺酶家族,在人類基因組中由12號染色體上的AICDA基因編碼,大小約為24kDa[6],可催化胞苷(C)去胺轉為尿苷(U)的反應,即將DNA上的C:G配對轉為U:G誤配,且因DNA複製時會將U視為T,最終會導致U:G轉為T:A的轉換突變[7][8]。U:G誤配也可能被細胞中的鹼基切除修復(BER)或錯誤配對修復(MMR)機制修補,BER途徑中此誤配可被尿嘧啶DNA醣苷基酶(UDG)識別而切除,形成AP位點,接著可能由DNA聚合酶η等易誤(error-prone)的聚合酶隨機補上鹼基而完成修補(短補丁修復),或將下游數個鹼基由內切酶切除後再合成新的核苷酸以完成修補(長補丁修復)[9];MMR途徑中,U:G誤配則會被MutSα複合體識別而被切除,再由易誤的聚合酶隨機補上鹼基,兩種修復機制皆可能造成突變[10]。DNA轉錄時暫時呈單股的狀態有利於活化誘導性胞苷去胺酶的催化反應[11][12]。
活化誘導性胞苷去胺酶最早於1999年由日本免疫學家本庶佑發現[13],此酵素在免疫系統中有重要功能,B細胞在淋巴結的生發中心進行親和力成熟的過程中,催化C去胺轉為U的反應以造成DNA斷裂,促進體細胞超突變、免疫球蛋白類型轉換和基因轉換等增加抗體多樣性的重要機制[14]。較新的研究顯示除B細胞外還有其他組織有表現活化誘導性胞苷去胺酶,且除催化C-U轉換之外,活化誘導性胞苷去胺酶還可催化5-甲基胞嘧啶去胺轉為胸腺嘧啶(T),因而有去甲基酶的功能,可能參與基因的表觀遺傳學調控[15][16]。
B細胞中有數種調控活化誘導性胞苷去胺酶活性的機制,例如此蛋白上有許多可能調控其活性的磷酸化位點[14]。此蛋白的表現異常與數種疾病有關,此基因的缺乏會導致第二型高免疫球蛋白M症候群[17],其過度表現則可能與數種B細胞淋巴瘤有關[14][18]。
參考文獻
[編輯]- ^ 與活化誘導胞苷脫氨酶相關的疾病;在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000111732 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000040627 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Entrez Gene: AICDA activation-induced cytidine deaminase.
- ^ Petersen-Mahrt, Svend K.; Harris, Reuben S.; Neuberger, Michael S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature. 2002-07-04, 418 (6893): 99–103 [2021-04-29]. ISSN 0028-0836. PMID 12097915. doi:10.1038/nature00862. (原始內容存檔於2021-02-05).
- ^ Q9GZX7 (AICDA_HUMAN). [26 January 2013]. (原始內容存檔於2021-06-04).
- ^ Pilzecker B, Jacobs H. Mutating for Good: DNA Damage Responses During Somatic Hypermutation.. Front Immunol. 2019, 10: 438. PMC 6423074
. PMID 30915081. doi:10.3389/fimmu.2019.00438.
- ^ Maul RW, Gearhart PJ. AID and somatic hypermutation.. Adv Immunol. 2010, 105: 159–91. PMC 2954419
. PMID 20510733. doi:10.1016/S0065-2776(10)05006-6.
- ^ Senavirathne G, Bertram JG, Jaszczur M, Chaurasiya KR, Pham P, Mak CH; et al. Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution.. Nat Commun. 2015, 6: 10209. PMC 4703863
. PMID 26681117. doi:10.1038/ncomms10209.
- ^ Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand.. Nat Immunol. 2003, 4 (5): 452–6. PMID 12692548. doi:10.1038/ni920.
- ^ Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO; et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.. J Biol Chem. 1999, 274 (26): 18470–6. PMID 10373455. doi:10.1074/jbc.274.26.18470.
- ^ 14.0 14.1 14.2 Robbiani DF, Nussenzweig MC. Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase.. Annu Rev Pathol. 2013, 8: 79–103. PMID 22974238. doi:10.1146/annurev-pathol-020712-164004.
- ^ Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming.. J Biol Chem. 2004, 279 (50): 52353–60. PMID 15448152. doi:10.1074/jbc.M407695200.
- ^ Dominguez PM, Shaknovich R. Epigenetic function of activation-induced cytidine deaminase and its link to lymphomagenesis.. Front Immunol. 2014, 5: 642. PMC 4270259
. PMID 25566255. doi:10.3389/fimmu.2014.00642.
- ^ Luo Z, Ronai D, Scharff MD. The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies. J. Allergy Clin. Immunol. 2004, 114 (4): 726–35; quiz 736. PMID 15480307. doi:10.1016/j.jaci.2004.07.049.
- ^ Lenz G, Staudt LM. Aggressive Lymphomas. N Engl J Med. 2010, 362 (15): 1417–29. PMC 7316377
. PMID 20393178. doi:10.1056/NEJMra0807082.
|