We recently provided the first evidence that the ASB2 gene encodes a novel ASB2 isoform, ASB2β, that is expressed in skeletal and cardiac muscle cells both during embryogenesis and in adult tissues. ASB2β is the specificity subunit of an active Cullin 5-RING (CRL) -type E3 ubiquitin ligase complex, and drives ubiquitin modification leading to proteasomal degradation of the actin binding protein Filamin B. Since ASB2β does not induce proteasomal degradation of Filamin A its targets are not exactly the same as ASB2α. This suggests that the two ASB2 isoforms have tissue specific functions through the tissue specific function of their substrates.We demonstrated that ASB2β is involved in in vitro myogenic differentiation through its effect on Filamin B degradation. Filamins through their binding to actin contribute to the organization and mechanical properties of the actin cytoskeleton. Moreover, they also act as scaffolds for signalling molecules.
The overall objective of this project is to further our understanding of the role of ASB2β during skeletal muscle development and also in mature skeletal muscle where it is still expressed. This work will be performed through the analysis of ASB2 conditional knock-out mice. Furthermore, we will decipher whether ASB2β through Filamin B degradation may regulate cytoskeleton rearrangements associated with myogenic differentiation and modulate cell signaling pathways critical to myogenic differentiation using cellular and molecular biology approaches.
Contact: Christel Moog-Lutz