Yoon Mi-Kyung, Ha Ji-Hyang, Lee Min-Sung, Chi Seung-Wook
Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB, Daejeon 305-806, Korea.
Structural Biology & Nanopore Research Laboratory, Functional Genomics Research Center, KRIBB, Daejeon 305-806; Department of Bio-Analytical Science, University of Science and Technology, Daejeon 305-350, Korea.
BMB Rep. 2015 Feb;48(2):81-90. doi: 10.5483/bmbrep.2015.48.2.255.
p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.
p73是p53肿瘤抑制蛋白的结构和功能同源物。与p53一样,p73诱导细胞凋亡和细胞周期停滞,并反式激活p53反应基因,赋予其肿瘤抑制活性。此外,p73在神经元发育和分化中具有独特作用。p73诱导的细胞凋亡的重要性在于其能够替代p53在各种p53发生突变或无活性的人类癌细胞中的促凋亡活性。尽管p73诱导的细胞凋亡在癌症治疗中非常重要,但对于p73诱导细胞凋亡的分子基础知之甚少。在本综述中,我们讨论了迄今为止报道的p73结构、p73与p53之间的详细结构比较,以及目前对p73诱导细胞凋亡的转录依赖性和非依赖性机制的理解。