Abdelmohsen Kotb, Lal Ashish, Kim Hyeon Ho, Gorospe Myriam
Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, Maryland 21224, USA.
Cell Cycle. 2007 Jun 1;6(11):1288-92. doi: 10.4161/cc.6.11.4299. Epub 2007 Jun 15.
The RNA-binding protein HuR can stabilize and/or regulate the translation of target mRNAs, thereby affecting the cellular responses to immune, proliferative, and damaging agents. Here, we discuss emerging evidence that HuR elicits a broad anti-apoptotic function through its influence on the expression of multiple target mRNAs. HuR was previously shown to bind to the mRNA encoding the apoptosome inhibitor prothymosin a(ProT alpha) and enhanced its translation and cytoplasmic abundance. More recently, HuR was shown to increase the stability of a target mRNA encoding the pro-survival deacetylase SIRT1. The discovery that HuR likewise binds to and promotes the expression of mRNAs encoding Bcl-2 and Mcl-1, two major anti-apoptotic effectors, strongly supports HuR's role as a key upstream coordinator of a constitutive pro-survival program.
RNA 结合蛋白 HuR 可稳定和/或调节靶 mRNA 的翻译,从而影响细胞对免疫、增殖和损伤因子的反应。在此,我们讨论新出现的证据,即 HuR 通过影响多个靶 mRNA 的表达引发广泛的抗凋亡功能。先前已表明 HuR 与编码凋亡小体抑制剂前胸腺素α(ProTα)的 mRNA 结合,并增强其翻译和细胞质丰度。最近,已表明 HuR 可增加编码促生存去乙酰化酶 SIRT1 的靶 mRNA 的稳定性。HuR 同样与编码两种主要抗凋亡效应因子 Bcl-2 和 Mcl-1 的 mRNA 结合并促进其表达,这一发现有力地支持了 HuR 作为组成性促生存程序关键上游协调者的作用。