Characterization of HSP90 isoforms in transformed bovine leukocytes infected with Theileria annulata.
Characterization of HSP90 isoforms in transformed bovine leukocytes infected with Theileria annulata.
复制标题
DOI：
10.1111/cmi.12669
复制
发表时间：
2017-03
影响因子：
3.4
通讯作者：
Shiels BR
中科院分区：
文献类型：
--
作者：
Kinnaird JH;Singh M;Gillan V;Weir W;Calder ED;Hostettler I;Tatu U;Devaney E;Shiels BR
HSP 90分子伴侣是细胞功能的重要调节剂，因为它们确保多个关键客户蛋白的适当构象。在原生动物环形泰勒虫（Theileria annulata）中鉴定出4种HSP 90亚型。对三种进行了部分表征，并确认了细胞质（TA 12105）、内质网（TA 06470）和顶质体（TA 10720）形式的定位。证明了重组TA 12105的ATP酶活性和与HSP 90抑制剂格尔德霉素的结合，并且所有三种天然形式都可以通过与格尔德霉素珠结合而在不同程度上分离。由于HSP 90的重要性，它被认为是一个潜在的治疗药物靶点。对唯一特异性杀泰勒虫药物的耐药性正在增加，设计靶向寄生虫的药物的一个挑战是限制对宿主的影响。一种体外细胞培养系统，可以比较未感染的牛细胞和T。利用感染了环孢霉的对应物来测试格尔德霉素和衍生物17-AAG的作用。T. annulata感染的细胞比未感染的细胞对格尔德霉素具有更大的耐受性，但对17-AAG表现出显著更高的敏感性。这些发现表明，寄生虫HSP 90同种型可以改变感染宿主细胞的药物敏感性，泰勒虫HSP 90家族的成员是值得进一步研究的潜在靶点。
HSP90 chaperones are essential regulators of cellular function, as they ensure the appropriate conformation of multiple key client proteins. Four HSP90 isoforms were identified in the protozoan parasite Theileria annulata. Partial characterization was undertaken for three and localization confirmed for cytoplasmic (TA12105), endoplasmic reticulum (TA06470), and apicoplast (TA10720) forms. ATPase activity and binding to the HSP90 inhibitor geldanamycin were demonstrated for recombinant TA12105, and all three native forms could be isolated to varying extents by binding to geldanamycin beads. Because it is essential, HSP90 is considered a potential therapeutic drug target. Resistance to the only specific Theileriacidal drug is increasing, and one challenge for design of drugs that target the parasite is to limit the effect on the host. An in vitro cell culture system that allows comparison between uninfected bovine cells and the T. annulata‐infected counterpart was utilized to test the effects of geldanamycin and the derivative 17‐AAG. T. annulata‐infected cells had greater tolerance to geldanamycin than uninfected cells yet exhibited significantly more sensitivity to 17‐AAG. These findings suggest that parasite HSP90 isoform(s) can alter the drug sensitivity of infected host cells and that members of the Theileria HSP90 family are potential targets worthy of further investigation.
影响因子：
--
作者：
Cilingir G;Broschat SL
通讯作者：
Broschat SL