S5a promotes the positive regulation of myogenic genes through ubiquitin-independent mechanisms involving inhibition of Id1 and the enhancement of DNA binding by MyoD and E12.
S5a promotes positive regulation of myogenic genes through ubiquitin-independent mechanisms involving inhibition of Id1.
Id proteins negatively regulate the dimerization, DNA binding, and biological properties of basic helix-loop-helix proteins. In a search for novel factors that interact with Id1, we identified a component of the 26 S proteasome, S5a, that has previously been implicated only in the recognition of ubiquitinated polypeptides destined for proteolysis. S5a interacts strongly with Id1, less strongly with the basic helix-loop-helix proteins MyoD and E12, and not at all with other Id proteins. S5a restores DNA binding by MyoD-Id1 and E12-Id1 heterodimers, enhances DNA binding by MyoD and E12 homodimers, and reverses Id1-mediated repression of the muscle creatine kinase promoter during myogenic differentiation. Mutagenesis experiments showed that amino acids flanking the helix-loop-helix domain plus three residues in the first helix of Id1 impart S5a recognition. This requires only the NH2-terminal half of S5a. S5a thus appears to promote the positive regulation of myogenic genes through ubiquitin-independent mechanisms involving inhibition of Id1 and the enhancement of DNA binding by MyoD and E12. This latter property may permit the selection of novel promoter binding sites during myogenesis.
Marcos A. Rossi (Sun,) reported a other. S5a was evaluated on DNA binding and Id1-mediated repression. S5a promotes the positive regulation of myogenic genes through ubiquitin-independent mechanisms involving inhibition of Id1 and the enhancement of DNA binding by MyoD and E12.