Intrinsically disordered proteins and phenotypic switching: Implications in cancer.

It is now well established that intrinsically disordered proteins (IDPs) that constitute a large part of the proteome across the three kingdoms, play critical roles in several biological processes including phenotypic switching. However, dysregulated expression of IDPs that engage in promiscuous interactions can lead to pathological states. In this chapter, using cancer as a paradigm, we discuss how IDP conformational dynamics and the resultant conformational noise can modulate phenotypic switching. Thus, contrary to the prevailing wisdom that phenotypic switching is highly deterministic (has a genetic underpinning) in cancer, emerging evidence suggests that non-genetic mechanisms, at least in part due to the conformational noise, may also be a confounding factor in phenotypic switching.