Exp Mol Med.  2016 Apr;48(4):e225. 10.1038/emm.2016.2.

Myosin heavy chain is stabilized by BCL-2 interacting cell death suppressor (BIS) in skeletal muscle

• Hong J
• Park JS
• Lee H
• Jeong J
• Yun HH
• Kim HY
• Ko YG
• Lee JH

• KMID: 2361512
• DOI: http://doi.org/10.1038/emm.2016.2

Abstract

BCL-2 interacting cell death suppressor (BIS), which is ubiquitously expressed, has important roles in various cellular processes, such as apoptosis, the cellular stress response, migration and invasion and protein quality control. In particular, BIS is highly expressed in skeletal and cardiac muscles, and BIS gene mutations result in human myopathy. In this study, we show that mRNA and protein levels of BIS were markedly increased during skeletal myogenesis in C2C12 cells and mouse satellite cells. BIS knockdown did not prevent the early stage of skeletal myogenesis, but did induce muscle atrophy and a decrease in the diameter of myotubes. BIS knockdown significantly suppressed the expression level of myosin heavy chain (MyHC) without changing the expression levels of myogenic marker proteins, such as Mgn, Cav-3 and MG53. In addition, BIS endogenously interacted with MyHC, and BIS knockdown induced MyHC ubiquitination and degradation. From these data, we conclude that molecular association of MyHC and BIS is necessary for MyHC stabilization in skeletal muscle.

MeSH Terms

Animals
Apoptosis
Cell Death*
Humans
Mice
Muscle Development
Muscle Fibers, Skeletal
Muscle, Skeletal*
Muscular Atrophy
Muscular Diseases
Myocardium
Myosin Heavy Chains*
Myosins*
Quality Control
RNA, Messenger
Ubiquitin
Ubiquitination
Myosin Heavy Chains
Myosins
RNA, Messenger
Ubiquitin