دورية أكاديمية

AMPK phosphorylates NAMPT to regulate NAD+ homeostasis under ionizing radiation

التفاصيل البيبلوغرافية
العنوان: AMPK phosphorylates NAMPT to regulate NAD+ homeostasis under ionizing radiation
المؤلفون: Xiaoyu Liao, Xiaoke Huang, Xin Li, Xuemei Qiu, Mi Li, Rui Liu, Tao He, Qingfeng Tang
المصدر: Open Biology, Vol 12, Iss 10 (2022)
بيانات النشر: The Royal Society, 2022.
سنة النشر: 2022
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: NAMPT, AMPK, NAD+, ionizing radiation, phosphorylation, Biology (General), QH301-705.5
الوصف: Radiation-induced oral mucositis is the most common complication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD+) is vital for DNA damage repair under ionizing radiation, through functioning as either the substrate for protein poly(ADP-ribosyl)ation at DNA break sites or the cofactor for multiple DNA repair-related enzymes, which therefore can result in a significant consumption of cellular NAD+ during DNA repair. Mammalian cells produce NAD+ mainly by recycling nicotinamide via the salvage pathway, in which the rate-limiting step is governed by nicotinamide phosphoribosyltransferase (NAMPT). However, whether NAMPT is co-opted under ionizing radiation to timely fine-tune NAD+ homeostasis remains elusive. Here we show that ionizing radiation evokes NAMPT activation within 30 min without apparent changes in its protein expression. AMPK rapidly phosphorylates NAMPT at S314 under ionizing radiation, which reinforces the enzymatic activity of NAMPT by increasing NAMPT binding with its substrate phosphoribosyl pyrophosphate (PRPP). AMPK-mediated NAMPT S314 phosphorylation substantially restores NAD+ level in the irradiated cells and facilitates DNA repair and cell viability. Our findings demonstrate a new post-translational modification-based signalling route, by which cells can rapidly orchestrate NAD+ metabolism to support DNA repair, thereby highlighting NAMPT as a potential target for the prevention of ionizing radiation-induced injuries.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2046-2441
Relation: https://doaj.org/toc/2046-2441
DOI: 10.1098/rsob.220213
URL الوصول: https://doaj.org/article/243a9ad8a2494359856467f4a5767239
رقم الأكسشن: edsdoj.243a9ad8a2494359856467f4a5767239
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20462441
DOI:10.1098/rsob.220213