Kulkarni Prakash, Salgia Ravi, Rangarajan Govindan
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
Department of Systems Biology, City of Hope National Medical Center, Duarte, CA, USA.
iScience. 2023 Jun 15;26(7):107109. doi: 10.1016/j.isci.2023.107109. eCollection 2023 Jul 21.
Phenotypic plasticity is the ability of individual genotypes to produce different phenotypes in response to environmental perturbations. We previously postulated how conformational noise emanating from conformational dynamics of intrinsically disordered proteins (IDPs) which is distinct from transcriptional noise, can contribute to phenotypic switching by rewiring the cellular protein interaction network. Since most transcription factors are IDPs, we posited that conformational noise is an integral component of transcriptional noise implying that IDPs may amplify total noise in the system either stochastically or in response to environmental changes. Here, we review progress in elucidating the details of the hypothesis. We highlight empirical evidence supporting the hypothesis, discuss conceptual advances that underscore its fundamental importance and implications, and identify areas for future investigations.
表型可塑性是指个体基因型在应对环境扰动时产生不同表型的能力。我们之前推测，由内在无序蛋白（IDP）的构象动力学产生的构象噪声，不同于转录噪声，它如何通过重新连接细胞蛋白质相互作用网络来促成表型转换。由于大多数转录因子是IDP，我们假定构象噪声是转录噪声的一个组成部分，这意味着IDP可能随机地或响应环境变化来放大系统中的总噪声。在这里，我们回顾了在阐明该假说细节方面取得的进展。我们强调支持该假说的经验证据，讨论强调其根本重要性和影响的概念性进展，并确定未来研究的领域。
