Cloning and initial characterization of the human DPYD gene promoter.
Cloning and initial characterization of the human DPYD gene promoter.
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人类 DPYD 基因启动子的克隆和初步表征。
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
H. McLeod
中科院分区：
文献类型：
--
作者：
E. Collie;S. J. Johnston;R. Powrie;G. Milano;M. Étienne;B. Rochat;G. Watson;H. McLeod
二氢嘧啶脱氢酶（DPD）是嘧啶碱基和嘧啶抗代谢物降解的限速酶。 DPD 活性降低与癌症患者 5-氟尿嘧啶 (5FU) 治疗的毒性以及儿科患者的神经系统异常有关。尽管已在 DPD 缺陷患者中鉴定出变异的 DPYD 等位基因，但它们并不能充分解释多态性 DPD 活性或体内相关的临床表型。 DPD 可能受到转录调节，因为 mRNA 水平与活性相关，并且在人体组织中受到差异性调节。人类 DPYD 基因的 1.85 kb 5' 侧翼区域被克隆，并在培养细胞中具有转录活性。对恒河猴和食蟹猴中这个 5' 侧翼区域的分析表明，人类和灵长类动物之间存在保守性 (>96%)。确定了普遍存在的和细胞特异性因子的假定结合位点。在一名 DPD 活性降低且 5FU 毒性严重的癌症患者中发现了一种破坏假定的 γ-干扰素反应元件的多态性。进一步深入了解 DPD 表达的调节可能会找到治疗与 DPD 缺乏相关的临床问题的新途径。
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and pyrimidine-based antimetabolites. Reduced DPD activity is associated with toxicity to 5-fluorouracil (5FU) therapy in cancer patients and with neurological abnormalities in paediatric patients. Although variant DPYD alleles have been identified in DPD-deficient patients, they do not adequately explain polymorphic DPD activity or associated clinical phenotypes in vivo. DPD may be transcriptionally regulated as mRNA levels correlate with activity and are differentially regulated in human tissues. A 1.85 kb 5' flanking region of the human DPYD gene was cloned and has transcriptional activity in cultured cells. Analysis of this 5' flanking region in rhesus and cynomolgus monkeys demonstrated conservation (>96%) between humans and primates. Putative binding sites for ubiquitous and cell-specific factors were identified. A polymorphism that disrupts a putative gamma-interferon response element was identified in a cancer patient with reduced DPD activity and severe 5FU toxicity. Further insight into regulation of DPD expression may identify new avenues for the treatment of clinical problems associated with DPD deficiency.
使用 5-氟尿嘧啶作为底物，二氢尿嘧啶脱氢酶活性在人体组织中的分布和抑制。
影响因子：
2
作者：
Ho,DH;Townsend,L;Luna,MA;Bodey,GP
通讯作者：
Bodey,GP
人生腱蛋白-X 的交替启动子和交替剪接，该基因的 5 和 3 末端埋藏在其他基因中。
影响因子：
3.5
作者：
Speek,M;Barry,F;Miller,WL
通讯作者：
Miller,WL