Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, United States.
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, United States.
Prog Mol Biol Transl Sci. 2019;166:63-84. doi: 10.1016/bs.pmbts.2019.03.013. Epub 2019 Apr 11.
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.
现在已经明确的是，构成三个领域中很大一部分蛋白质组的无规则蛋白质（IDP）在包括表型转换在内的几个生物过程中起着关键作用。然而，参与杂乱相互作用的 IDP 的失调表达可能导致病理状态。在本章中，我们以癌症为例，讨论了 IDP 构象动力学和由此产生的构象噪声如何调节表型转换。因此，与表型转换在癌症中具有高度确定性（具有遗传基础）的普遍观点相反，新出现的证据表明，非遗传机制，至少部分由于构象噪声，也可能是表型转换中的一个混杂因素。
