Traf7, a MyoD1 transcriptional target, regulates nuclear factor-κB activity during myogenesis.
We have identified the E3 ligase Traf7 as a direct MyoD1 target and show that cell cycle exit-an early event in muscle differentiation-is linked to decreased Traf7 expression. Depletion of Traf7 accelerates myogenesis, in part through downregulation of nuclear factor-κB (NF-κB) activity. We used a proteomic screen to identify NEMO, the NF-κB essential modulator, as a Traf7-interacting protein. Finally, we show that ubiquitylation of NF-κB essential modulator is regulated exclusively by Traf7 activity in myoblasts. Our results suggest a new mechanism by which MyoD1 function is coupled to NF-κB activity through Traf7, regulating the balance between cell cycle progression and differentiation during myogenesis.
Department of Pathology, New York University School of Medicine, New York 10016, USA.
Mary
M
Tsikitis
Diego
D
Acosta-Alvear
Alexandre
A
Blais
Eric I
EI
Campos
William S
WS
Lane
Irma
I
Sánchez
Brian D
BD
Dynlacht
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D017570:MyoD Protein / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D014158:Transcription, Genetic; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
D047908:Intracellular Signaling Peptides and Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C514981:NEMO protein, mouse; D016328:NF-kappa B; D016160:Retinoblastoma Protein; C486461:Traf7 protein, mouse; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D025801:Ubiquitin; D019938:Cyclin D1; D051550:I-kappa B Kinase