Degradation of an ubiquitin-conjugated protein is associated with myoblast differentiation in primary cell culture.
At the early stages of myogenesis, myoblasts fuse to form multinucleated myotubes. This morphological differentiation is the result of dynamic changes in gene regulation and expression. The ubiquitin proteasome-dependent pathway has been reported to play an important role in many aspects of cellular functions such as regulation of growth and cell cycle progression. In this study, we showed that the amount of mRNA's corresponding to the iota subunit of the 20S proteasome, the level of the S4 subunit of the 19S complex and the 20S and 26S proteasomes peptidase activities increased during myoblast fusion. Cell permeable 20S proteasome inhibitor prevented fusion with concomitant accumulation of ubiquitin-conjugated protein. On the other hand, inhibition of ubiquitin ligase E3 enzymes prevented the formation of ubiquitin conjugate and decreased the fusion process. These results strongly support the involvement of the ubiquitin-proteasome proteolytic pathway in the events leading to myoblast fusion.
Gardrat
F
F
Laboratoire de Biochimie et Technologie des Aliments, ISTAB Avenue des Facultés, Talence, France.
Montel
V
V
Raymond
J
J
Azanza
J L
JL
D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion / Q000187:drug effects; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D007783:Lactones / Q000494:pharmacology; D008025:Ligases / Q000037:antagonists & inhibitors; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007783:Lactones; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; C098869:clasto-lactacystin beta-lactone; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008025:Ligases