TRIM72 negatively regulates myogenesis via targeting insulin receptor substrate-1.
Lipid rafts have been known to be platforms to initiate cellular signal transduction of insulin-like growth factor (IGF) inducing skeletal muscle differentiation and hypertrophy. Here, tripartite motif 72 (TRIM72), with a really interesting new gene (RING)-finger domain, a B-box, two coiled-coil domains, and a SPRY (SPla and RYanodine receptor) domain, was revealed to be predominantly expressed in the sarcolemma lipid rafts of skeletal and cardiac muscles. Adenoviral TRIM72 overexpression prevented but RNAi-mediated TRIM72 silencing enhanced C2C12 myogenesis by modulating the IGF-induced insulin receptor substrate-1 (IRS-1) activation through the molecular association of TRIM72 with IRS-1. Furthermore, myogenic activity was highly enhanced with increased IGF-induced Akt activation in the satellite cells of TRIM72(-/-) mice, compared to those of TRIM72+/+ mice. Because TRIM72 promoter analysis shows that two proximal E-boxes in TRIM72 promoter were essential for MyoD- and Akt-dependent TRIM72 transcription, we can conclude that TRIM72 is a novel antagonist of IRS-1, and is essential as a negative regulator of IGF-induced muscle differentiation.
College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
C S
CS
Lee
J-S
JS
Yi
S-Y
SY
Jung
B-W
BW
Kim
N-R
NR
Lee
H-J
HJ
Choo
S-Y
SY
Jang
J
J
Han
S-G
SG
Chi
M
M
Park
J-H
JH
Lee
Y-G
YG
Ko
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
D002352:Carrier Proteins; D055504:Insulin Receptor Substrate Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt