Chen C Y, Del Gatto-Konczak F, Wu Z, Karin M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Science. 1998 Jun 19;280(5371):1945-9. doi: 10.1126/science.280.5371.1945.
Signaling pathways that stabilize interleukin-2 (IL-2) messenger RNA (mRNA) in activated T cells were examined. IL-2 mRNA contains at least two cis elements that mediated its stabilization in response to different signals, including activation of c-Jun amino-terminal kinase (JNK). This response was mediated through a cis element encompassing the 5' untranslated region (UTR) and the beginning of the coding region. IL-2 transcripts lacking this 5' element no longer responded to JNK activation but were still responsive to other signals generated during T cell activation, which were probably sensed through the 3' UTR. Thus, multiple elements within IL-2 mRNA modulate its stability in a combinatorial manner, and the JNK pathway controls turnover as well as synthesis of IL-2 mRNA.
对活化T细胞中稳定白细胞介素-2(IL-2)信使核糖核酸(mRNA)的信号通路进行了研究。IL-2 mRNA包含至少两个顺式元件,这些元件介导其在不同信号响应下的稳定性,包括c-Jun氨基末端激酶(JNK)的激活。这种反应是通过一个包含5'非翻译区(UTR)和编码区起始部分的顺式元件介导的。缺乏这个5'元件的IL-2转录本不再对JNK激活作出反应,但仍对T细胞激活过程中产生的其他信号有反应,这些信号可能是通过3'UTR感知到的。因此,IL-2 mRNA中的多个元件以组合方式调节其稳定性,并且JNK通路控制IL-2 mRNA的周转以及合成。