Joseph B, Orlian M, Furneaux H
Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Biol Chem. 1998 Aug 7;273(32):20511-6. doi: 10.1074/jbc.273.32.20511.
The Elav-like proteins are specific mRNA-binding proteins that regulate mRNA stability. The neuronal members of this family (HuD, HuC, and Hel-N1) are required for neuronal differentiation. In this report, using purified HuD protein we have localized a high affinity HuD binding site to a 42-nucleotide region within a U-rich tract in the 3'-untranslated region p21(waf1) mRNA. The binding of HuD to this site is readily displaced by an RNA oligonucleotide encoding the HuD binding site of c-fos. The sequence of this binding site is well conserved in human, mouse, and rat p21(waf1) mRNA. p21(waf1) is an inhibitor of cyclin-dependent kinases and proliferating cell nuclear antigen and induces cell cycle arrest at G1/S, a requisite early step in cell differentiation. The identification of an Elav-like protein binding site in the 3'-untranslated region of p21(waf1) provides a novel link between the induction of differentiation, mRNA stability, and the termination of the cell cycle.
Elav样蛋白是一类特异性的mRNA结合蛋白，可调节mRNA的稳定性。该家族的神经元成员（HuD、HuC和Hel-N1）是神经元分化所必需的。在本报告中，我们使用纯化的HuD蛋白，将一个高亲和力的HuD结合位点定位到p21（waf1）mRNA 3'-非翻译区富含U的区域内的一个42个核苷酸的区域。HuD与该位点的结合很容易被编码c-fos的HuD结合位点的RNA寡核苷酸所取代。该结合位点的序列在人、小鼠和大鼠的p21（waf1）mRNA中高度保守。p21（waf1）是细胞周期蛋白依赖性激酶和增殖细胞核抗原的抑制剂，可诱导细胞周期在G1/S期停滞，这是细胞分化早期的一个必要步骤。在p21（waf1）的3'-非翻译区鉴定出一个Elav样蛋白结合位点，为分化诱导、mRNA稳定性和细胞周期终止之间提供了一个新的联系。
