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Category | CDBセミナー |
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Date and Time | 2016-12-14 16:00 - 17:00 |
Venue | Auditorium C1F |
Speaker | Shuhei Nakamura |
Affiliation | Department of Genetics, Graduate School of Medicine, Osaka University |
Title | An extensive HLH transcription factor network promoting longevity in response to signals from the gonad |
Poster | click here to download(PDF) |
Host | Tomoya Kitajima |
Summary | The reproductive system is responsible for procreation but also affects life span in many species. In C. elegans, removal of the germline extends lifespan up to 60% (termed gonadal longevity). Several transcription factors regulate longevity arising from germline removal, yet how they work together is unknown. We have recently identified a Myc-like HLH-transcription factor network comprised of Mondo/Max-like complex (MML-1/MXL-2) required for longevity induced by germline removal, as well as by reduced TOR (Target Of Rapamycin), insulin/IGF signaling, and mitochondrial function. Germline removal triggers MML-1 nuclear localization and activity. Surprisingly MML-1 regulates nuclear localization and activity of HLH-30/TFEB, a convergent regulator of autophagy, lysosome biogenesis and longevity, by downregulating TOR signaling via LARS-1/leucyl-tRNA synthase. HLH-30 also upregulates MML-1 upon germline removal. Mammalian MondoA/B and TFEB show similar mutual regulation. MML-1/MXL-2 and HLH-30 transcriptomes show both shared and distinct outputs including MDL-1/MAD-like HLH factor required for longevity. These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. |