title: Fas-Associated Protein with Death Domain Regulates Notch Signaling during Muscle Regeneration.
abstract: Notch signaling plays critical roles during myogenesis by promoting the proliferation and inhibiting the differentiation of myogenic progenitors. However, the mechanism of the temporal regulation of Notch signaling during the myogenic lineage progression remains elusive. In the present study, we show that a constitutively phosphoryl-mimicking mutation of Fas-associated death domain (FADD-D) enhances Notch-1 signaling and compromises Wnt signaling in both cultured myoblasts and regenerating muscles, which results in inhibited myogenic differentiation and muscle regeneration. Inhibition of Notch signaling recovers the regeneration ability in injured FADD-D muscles through rescuing Wnt signaling. Furthermore, we found that protein kinase Cα mediates FADD-D-induced Notch-1 signaling by stabilizing Notch-1. Collectively, these data identify a novel mechanism for the temporal regulation of Notch signaling during myogenic lineage progression and muscle regeneration.
authors: State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, PR China.
authors: Rong
authors: R
authors: Zhang
authors: Lu
authors: L
authors: Wang
authors: Liangqiang
authors: L
authors: He
authors: Bingya
authors: B
authors: Yang
authors: Chun
authors: C
authors: Yao
authors: Pan
authors: P
authors: Du
authors: Qiang
authors: Q
authors: Xu
authors: Wei
authors: W
authors: Cheng
authors: Zi-Chun
authors: ZC
authors: Hua
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D006801:Humans; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D055550:Protein Stability; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D051880:Receptors, Notch; D051176:beta Catenin; D011494:Protein Kinases