Naseer Faiza, Saleem Mohammad
Shifa College of Pharmaceutical Sciences, Shifa Tameer e Millat University, Islamabad, Pakistan.
Faculty of Pharmaceutical Sciences, Punjab University, Lahore, Pakistan.
Oncol Rev. 2019 Jul 24;13(2):421. doi: 10.4081/oncol.2019.421. eCollection 2019 Jul 22.
A p73 is a new member of p53 family of transcription factor, having two types. First is TAp73, transcriptionally active and expressed upstream promoter as a tumor suppressor and vital apoptotic inductor, it also has a key role in cell cycle arrest/differentiation and Second is ΔNp73 that is transcriptionally inactive and expressed downstream regulator as oncogenes. Both types are expressed in various isoforms, which originate from alternative splicing events at the C-terminus. Upon DNA damage, posttranslational modifications cause conformational changes in various amino acid residues induction or inhibition of various proteins, which are present in the structural domains of p73. These modifications may cause up- or down-regulation of p73 expression levels, as well as alters the transcriptional activity and/or stability of the protein. In this review, we have made an effort to assemble all existing data regarding the role of p73, its modification and after effects in cancer.
p73是转录因子p53家族的新成员,有两种类型。第一种是TAp73,具有转录活性,作为肿瘤抑制因子和重要的凋亡诱导剂在上游启动子处表达,它在细胞周期停滞/分化中也起关键作用;第二种是ΔNp73,转录无活性,作为癌基因在下游调节区表达。这两种类型都以多种异构体形式表达,这些异构体源于C末端的可变剪接事件。DNA损伤时,翻译后修饰会导致p73结构域中各种氨基酸残基的构象变化,从而诱导或抑制各种蛋白质。这些修饰可能导致p73表达水平的上调或下调,以及改变蛋白质的转录活性和/或稳定性。在本综述中,我们努力收集了所有关于p73在癌症中的作用、其修饰及后续影响的现有数据。