Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kang, Hyun Tae | - |
dc.contributor.author | Park, Joon Tae | - |
dc.contributor.author | Choi, Kobong | - |
dc.contributor.author | Kim, Yongsub | - |
dc.contributor.author | Choi, Hyo Jei Claudia | - |
dc.contributor.author | Jung, Chul Won | - |
dc.contributor.author | Lee, Young-Sam | - |
dc.contributor.author | Park, Sang Chul | - |
dc.date.available | 2017-08-10T08:11:57Z | - |
dc.date.created | 2017-08-09 | - |
dc.date.issued | 2017-06 | - |
dc.identifier.issn | 1552-4450 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/4162 | - |
dc.description.abstract | Senescence, defined as irreversible cell-cycle arrest, is the main driving force of aging and age-related diseases. Here, we performed high-throughput screening to identify compounds that alleviate senescence and identified the ataxia telangiectasia mutated (ATM) inhibitor KU-60019 as an effective agent. To elucidate the mechanism underlying ATM's role in senescence, we performed a yeast two-hybrid screen and found that ATM interacted with the vacuolar ATPase V-1 subunits ATP6V1E1 and ATP6V1G1. Specifically, ATM decreased E-G dimerization through direct phosphorylation of ATP6V1G1. Attenuation of ATM activity restored the dimerization, thus consequently facilitating assembly of the V-1 and V-0 domains with concomitant reacidification of the lysosome. In turn, this reacidification induced the functional recovery of the lysosome/autophagy system and was coupled with mitochondrial functional recovery and metabolic reprogramming. Together, our data reveal a new mechanism through which senescence is controlled by the lysosomal-mitochondrial axis, whose function is modulated by the fine-tuning of ATM activity. | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Chemical screening identifies ATM as a target for alleviating senescence | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/nchembio.2342 | - |
dc.identifier.scopusid | 2-s2.0-85016112680 | - |
dc.identifier.bibliographicCitation | Nature Chemical Biology, v.13, no.6, pp.616 - + | - |
dc.subject.keywordPlus | Acidification | - |
dc.subject.keywordPlus | Activation | - |
dc.subject.keywordPlus | Autophagy | - |
dc.subject.keywordPlus | Disease | - |
dc.subject.keywordPlus | Epithelial Cells | - |
dc.subject.keywordPlus | Kinase | - |
dc.subject.keywordPlus | Lifespan | - |
dc.subject.keywordPlus | Lysosomal Ph | - |
dc.subject.keywordPlus | Mitochondria | - |
dc.subject.keywordPlus | Yeast Vacuolar Atpase | - |
dc.citation.endPage | + | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 616 | - |
dc.citation.title | Nature Chemical Biology | - |
dc.citation.volume | 13 | - |
There are no files associated with this item.