کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904088 | 1086558 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Degradation of AF1Q by chaperone-mediated autophagy
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کلمات کلیدی
CMAHBSS3-MA6-ANMacroautophagyHSPA8AMLlysosome-associated membrane protein 2a3-methyladenine - 3-متیل آدنین6-aminonicotinamide - 6-آمینونیکوتامینیدChaperone-mediated autophagy - Autofagy متعهد ChaperoneHanks balanced salt solution - Hanks محلول نمک را تعویض می کندProtein degradation - تخریب پروتئینacute myeloid leukemia - لوسمی حاد میلوئیدی یا به اختصار AMLChloroquine - کلروکین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 327, Issue 1, 10 September 2014, Pages 48-56
Journal: Experimental Cell Research - Volume 327, Issue 1, 10 September 2014, Pages 48-56
نویسندگان
Peng Li, Min Ji, Fei Lu, Jingru Zhang, Huanjie Li, Taixing Cui, Xing Li Wang, Dongqi Tang, Chunyan Ji,