Journal of Cachexia, Sarcopenia and Muscle (JCSM) - Abstract


UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes

Cécile Polge, Roza Leulmi, Marianne Jarzaguet, Agnes Claustre1, Lydie Combaret, Daniel Béchet, Anne-Elisabeth Heng, Didier Attaix, Daniel Taillandier

Background

Skeletal muscle protein loss is an adaptive response to various patho-physiological situations, and the ubiquitin proteasome system (UPS) is responsible for the degradation of the bulk of muscle proteins. The role of E2 ubiquitin-conjugating enzymes is still poorly understood in skeletal muscle.

Methods

We screened for E2s expression levels in C2C12 myotubes submitted to the catabolic glucocorticoid dexamethasone (Dex).

Results

One micromolar Dex induced an accumulation of proteasome substrates (polyUb conjugates) and an overexpression of the muscle-specific E3 ligase MuRF1 and of six E2 enzymes, UBE2A, UBE2B, UBE2D1, UBE2D2, UBE2G1, and UBE2J1. However, only MuRF1 and UBE2B were sensitive to mild catabolic conditions (0.16 μM Dex). UBE2B knockdown induced a sharp decrease of total (−18%) and K48 (−28%) Ub conjugates, that is, proteasome substrates, indicating an important role of UBE2B in the overall protein breakdown in catabolic myotubes.

Conclusions

Interestingly, these results indicate an important role of UBE2B on muscle protein homeostasis during catabolic conditions.


Polge, C., Leulmi, R., Jarzaguet, M., Claustre, A., Combaret, L., Béchet, D., Heng, A. -E., Attaix, D., and Taillandier, D. (2016) UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes. Journal of Cachexia, Sarcopenia and Muscle, 7: 377–387. doi: 10.1002/jcsm.12060.