A mutation in aminopeptidase N (CD13) isolated from a patient suffering from leukemia leads to an arrest in the endoplasmic reticulum
A mutation in aminopeptidase N (CD13) isolated from a patient suffering from leukemia leads to an arrest in the endoplasmic reticulum
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DOI：
10.1074/jbc.m511364200
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发表时间：
2006-04-28
影响因子：
4.8
通讯作者：
Lendeckel, U
中科院分区：
文献类型：
--
作者：
Alfalah, M;Krahn, MP;Lendeckel, U
人氨肽酶N（APN）被用作造血系统恶性疾病中骨髓单核细胞的常规标志物。其基因和表面表达在恶性转化、炎症或T细胞活化的情况下增加，而正常B和静息T细胞缺乏可检测的APN蛋白表达。在这项研究中，我们阐明了细胞内的分布，表达模式，和酶活性的APN基因的编码区的天然突变。在生理温度下，突变蛋白是无酶活性的，在内质网中作为富含甘露糖的多肽存在，并最终通过内质网相关的降解途径降解。它部分显示了温度敏感突变体的独特行为，允许温度为32摄氏度，导致高尔基体区室的正确分选，伴随着适当的糖基化的获得，但没有到达细胞表面膜，也没有恢复其酶活性。由于携带这种突变的患者患有白血病，可能的联系，白血病的发病机制进行了讨论。
Human aminopeptidase N (APN) is used as a routine marker for myelomonocytic cells in hematopoietic malignant disorders. Its gene and surface expressions are increased in cases of malignant transformation, inflammation, or T cell activation, whereas normal B and resting T cells lack detectable APN protein expression. In this study we elucidated the intracellular distribution, expression pattern, and enzymatic activity of a naturally occurring mutation in the coding region of the APN gene. At physiological temperatures the mutant protein is enzymatically inactive, persists as a mannose-rich polypeptide in the endoplasmic reticulum, and is ultimately degraded by an endoplasmic reticulum-associated degradation pathway. It shows in part the distinct behavior of a temperature-sensitive mutant with a permissive temperature of 32 degrees C, leading to correct sorting of the Golgi compartment accompanied by the acquisition of proper glycosylation but without reaching the cell-surface membrane and without regaining its enzymatic activity. Because the patient bearing this mutation suffered from leukemia, possible links to the pathogenesis of leukemia are discussed.