کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10157668 | 1666473 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS
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کلمات کلیدی
MSTVAPBSALSFused in sarcoma (FUS)VCPTDP-43DAPIHRPFUs - FUSHpo - HPOhippo - اسب آبیamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکSporadic amyotrophic lateral sclerosis - اسکلروز جانبی جانبی آمیوتروفی اسپورادیکfamilial amyotrophic lateral sclerosis - اسکلروز جانبی جانبی آمیوتروفی فامیلیamyotrophic lateral sclerosis (ALS) - اسکلروز جانبی جانبی آمیوتروفیک (ALS)ALS - بیماری اسکلروز جانبی آمیوتروفیکfALS - جعل اسنادfused in sarcoma - در سارکوم متصل شده استCNS - دستگاه عصبی مرکزیCabeza - سرcentral nervous system - سیستم عصبی مرکزیCaz - موردDrosophila - مگس سرکهHorseradish peroxidase - پراکسیداز هوررادیشValosin-containing protein - پروتئین حاوی والوسین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mutations in the Fused in Sarcoma (FUS) gene have been identified in familial ALS in human. Drosophila contains a single ortholog of human FUS called Cabeza (Caz). We previously established Drosophila models of ALS targeted to Caz, which developed the locomotive dysfunction and caused anatomical defects in presynaptic terminals of motoneurons. Accumulating evidence suggests that ALS and cancer share defects in many cellular processes. The Hippo pathway was originally discovered in Drosophila and plays a role as a tumor suppressor in mammals. We aimed to determine whether Hippo pathway genes modify the ALS phenotype using Caz knockdown flies. We found a genetic link between Caz and Hippo (hpo), the Drosophila ortholog of human Mammalian sterile 20-like kinase (MST) 1 and 2. Loss-of-function mutations of hpo rescued Caz knockdown-induced eye- and neuron-specific defects. The decreased Caz levels in nuclei induced by Caz knockdown were also rescued by loss of function mutations of hpo. Moreover, hpo mRNA level was dramatically increased in Caz knockdown larvae, indicating that Caz negatively regulated hpo. Our results demonstrate that hpo, Drosophila MST, is a novel modifier of Drosophila FUS. Therapeutic targets that inhibit the function of MST could modify the pathogenic processes of ALS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 371, Issue 2, 15 October 2018, Pages 311-321
Journal: Experimental Cell Research - Volume 371, Issue 2, 15 October 2018, Pages 311-321
نویسندگان
Yumiko Azuma, Takahiko Tokuda, Yukie Kushimura, Itaru Yamamoto, Ikuko Mizuta, Toshiki Mizuno, Masanori Nakagawa, Morio Ueyama, Yoshitaka Nagai, Yasushi Iwasaki, Mari Yoshida, Duojia Pan, Hideki Yoshida, Masamitsu Yamaguchi,