التفاصيل البيبلوغرافية
| العنوان: |
Impacts of HDAC4-MAP1S Interaction on Autophagy and Diseases |
| المؤلفون: |
Yue, Fei |
| المساهمون: |
Liu, Leyuan, Wang, Fen, Zhang, Dekai, Shen, Qiang |
| سنة النشر: |
2019 |
| المجموعة: |
Texas A&M University Digital Repository |
| مصطلحات موضوعية: |
HDAC4, MAP1S, autophagy, Huntington's Diseases, aging, Hepatocellular Carcinomas |
| الوصف: |
Autophagy is a cellular process to sequester cytoplasmic components for delivery to lysosomes for subsequent degradation, and plays important roles in aging and aging-associated pathogenesis. MAP1S is a ubiquitously distributed autophagy activator, which directly binds to the autophagosome marker LC3, accelerates autophagy initiation and degradation. Elucidating the mechanism of MAP1S-mediated autophagy can generate insights to control aging and aging-associated diseases. We discover that the acetylation of MAP1S maintains the stability of MAP1S protein and promotes autophagy. MAP1S interacts with HDAC4 via an HDAC4-binding domain (HBD). HDAC4 destabilizes MAP1S via deacetylation and suppresses autophagic flux. Huntington’s disease is a fatal progressive neurodegenerative disorder caused by the accumulation of aggregation-prone mutant Huntingtin protein (mHTT). Utilizing cell line stably expressing GFP-mHTT, we demonstrate that an overexpression of HDAC4 causes accumulation of mHTT aggregates by inhibiting MAP1S-mediated autophagy. Either suppression of HDAC4 or overexpression of HBD promotes the stability of MAP1S, and enhances MAP1S-regulated autophagic clearance of mHTT aggregates. This reveals a new potential strategy to treat Huntington’s disease by interrupting HDAC4-MAP1S interaction. Spermidine is a polyamine that activates autophagy and enhances longevity in some model systems. MAP1S-mediated autophagy helps mice maintain their lifespans and suppresses diethylnitrosamine-induced hepatocellular carcinomas. Thus, we hypothesize that spermidine regulates MAP1S-mediated autophagy to prolong lifespans and suppress hepatocarcinogenesis. Our results indicate that spermidine activates autophagy by depleting cytosolic HDAC4 to reduce HDAC4-MAP1S interaction, and enhance the acetylation of MAP1S. Wild-type mice drinking spermidine-containing water have higher levels of MAP1S and autophagy activity, and extended lifespans, compared to wild-type mice drinking water; whereas MAP1S^-/- mice drinking spermidine have ... |
| نوع الوثيقة: |
thesis |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
https://hdl.handle.net/1969.1/174231Test |
| الإتاحة: |
https://hdl.handle.net/1969.1/174231Test |
| رقم الانضمام: |
edsbas.81B15879 |
| قاعدة البيانات: |
BASE |
