Secretome Analysis of Skeletal Myogenesis Using SILAC and Shotgun Proteomics
Figure 2
Skeletal muscle differentiation at the microscopic and molecular level. (a) During myogenesis, mononucleated myoblast proliferate, followed by cell-cycle exit, and fusion to form multinucleated myotube; (b) during proliferation, at the molecular level, active CDK could trigger myoblast proliferation by phosphorylating and subjecting pRb to degradation, in which E2F transcription factor is free from the inhibitory effect of pRb and elicits the proliferation of myoblasts. Simultaneously, CDK can also block myoblasts from differentiation via the phosphorylation-induced degradation of MRF. As a consequence, E protein by itself cannot drive the differentiation program; (c) upon cell-cell contact, m-cadherin is activated, by which CDKI is induced. This in turn inhibits CDK from phosphorylating its downstream substrates: pRb and MRF. Hence, both pRb and MRF are exempted from degradation, in which the former can withdraw the myoblasts from the cell cycle by inhibiting E2F transcription factor from activating the proliferation-associated events, whereas the latter complexes with E protein, myogenic co-activator MEF2, and the chromatin remodeling molecule HATs, in an effort to evoke the differentiation program of myoblasts synergistically. Phosphate groups were indicated as “PO4”.
