Harper Kelly A, Tyson-Capper Alison J
Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Biochem Soc Trans. 2008 Jun;36(Pt 3):543-5. doi: 10.1042/BST0360543.
Overexpression of the enzyme COX-2 (cyclo-oxygenase-2) is associated with various pathophysiological conditions, including inflammatory diseases and different cancers. Increased synthesis of COX-2 in fetal membranes and the myometrium is also linked with the onset of term and preterm labour. COX-2 gene regulation is controlled at various levels including gene transcription and post-transcriptional events. The present article focuses on the complexity of COX-2 gene regulation and reviews current concepts that highlight: (i) transcription of COX-2 is induced rapidly and transiently in response to a plethora of stimuli; (ii) COX-2 mRNA stability and translational efficiency is governed by multiple regulatory elements within the 3'-untranslated region; (iii) specific microRNAs and RNA-binding proteins influence COX-2 mRNA stability; and (iv) regulation of COX-2 involves alternative polyadenylation.
酶COX-2(环氧化酶-2)的过表达与多种病理生理状况相关,包括炎症性疾病和不同类型的癌症。胎膜和子宫肌层中COX-2合成的增加也与足月分娩和早产的发生有关。COX-2基因调控在多个层面受到控制,包括基因转录和转录后事件。本文重点关注COX-2基因调控的复杂性,并综述当前的概念,这些概念强调:(i)COX-2的转录在受到大量刺激时迅速且短暂地被诱导;(ii)COX-2 mRNA的稳定性和翻译效率由3'非翻译区内的多个调控元件决定;(iii)特定的微小RNA和RNA结合蛋白影响COX-2 mRNA的稳定性;(iv)COX-2的调控涉及可变聚腺苷酸化。