Marques Mayra A, de Andrade Guilherme C, Silva Jerson L, de Oliveira Guilherme A P
Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, National Center of Nuclear Magnetic Resonance Jiri Jonas, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Front Mol Biosci. 2022 Aug 25;9:944955. doi: 10.3389/fmolb.2022.944955. eCollection 2022.
The p53 protein is a pleiotropic regulator working as a tumor suppressor and as an oncogene. Depending on the cellular insult and the mutational status, p53 may trigger opposing activities such as cell death or survival, senescence and cell cycle arrest or proliferative signals, antioxidant or prooxidant activation, glycolysis, or oxidative phosphorylation, among others. By augmenting or repressing specific target genes or directly interacting with cellular partners, p53 accomplishes a particular set of activities. The mechanism in which p53 is activated depends on increased stability through post-translational modifications (PTMs) and the formation of higher-order structures (HOS). The intricate cell death and metabolic p53 response are reviewed in light of gaining stability PTM and HOS formation in health and disease.
p53蛋白是一种多效调节剂,兼具肿瘤抑制因子和癌基因的作用。根据细胞所受损伤及突变状态,p53可能引发相反的活动,如细胞死亡或存活、衰老、细胞周期停滞或增殖信号、抗氧化或促氧化激活、糖酵解或氧化磷酸化等。通过增强或抑制特定靶基因或直接与细胞伴侣相互作用,p53实现了一系列特定的活动。p53被激活的机制取决于通过翻译后修饰(PTM)增加稳定性以及高阶结构(HOS)的形成。鉴于在健康和疾病状态下稳定性的获得、PTM和HOS的形成,对复杂的细胞死亡和代谢性p53反应进行了综述。