Peptide-based modulation of helix-loop-helix proteins

The helix-loop-helix (HLH) fold is the characteristic dimerization domain of the so called HLH transcription factors. This domain triggers the formation of homo- and heterodimers upon building of a parallel four-helix bundle. The Id proteins are neg. HLH transcription factors that control cell proliferation and differentiation during development and tumorigenesis. We are interested in the inhibition of Id protein dimerization with their endogenous partners, including the basic-HLH E and MyoD proteins. Our approach exploits peptide constructs targeting the HLH region of the Id proteins. Herein we will present our first results on the identification of short amino acid sequences able to interact with the Id HLH domain and to modulate the Id protein levels in a smooth muscle cell system.