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Therapeutic Interventions of Cancers Using Intrinsically Disordered Proteins as Drug Targets: c-Myc as Model System.

The concept of protein intrinsic disorder has taken the driving seat to understand regulatory proteins in general. Reports suggest that in mammals nearly 75% of signalling proteins contain long disordered regions with greater than 30 amino acid residues. Therefore, intrinsically disordered proteins (IDPs) have been implicated in several human diseases and should be considered as potential novel drug targets. Moreover, intrinsic disorder provides a huge multifunctional capability to hub proteins such as c-Myc and p53. c-Myc is the hot spot for understanding and developing therapeutics against cancers and cancer stem cells. Our past understanding is mainly based on in vitro and in vivo experiments conducted using c-Myc as whole protein. Using the reductionist approach, c-Myc oncoprotein has been divided into structured and disordered domains. A wealth of data is available dealing with the structured perspectives of c-Myc, but understanding c-Myc in terms of disordered domains has just begun. Disorderness provides enormous flexibility to proteins in general for binding to numerous partners. Here, we have reviewed the current progress on understanding c-Myc using the emerging concept of IDPs.

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