期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 28, 期 1, 页码 93-107出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00973-07
关键词
-
资金
- Intramural NIH HHS Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [Z01AG000511, ZIAAG000392, ZIAAG000511, Z01AG000392] Funding Source: NIH RePORTER
The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) are tightly controlled. Here, we investigated the post-transcriptional regulation of HIF-1 alpha expression in human cervical carcinoma HeLa cells responding to the hypoxia mimetic CoCl2. Undetectable in untreated cells, HIF-1 alpha levels increased dramatically in CoCl2-treated cells, while HIF-1 alpha mRNA levels were unchanged. HIF-1 alpha translation was potently elevated by CoCl, treatment, as determined by de novo translation analysis and by monitoring the polysomal association of HIF-1 alpha mRNA. An internal ribosome entry site in the HIF-1 alpha 5' untranslated region (UTR) was found to enhance translation constitutively, but it did not further induce translation in response to CoCl, treatment. Instead, we postulated that RNA-binding proteins HuR and PTB, previously shown to bind HIF-1 alpha mRNA, participated in its translational upregulation after CoCl2 treatment. Indeed, both RNA-binding proteins were found to bind HIF-1 alpha mRNA in a CoCl2-inducible manner as assessed by immunoprecipitation of endogenous ribonucleoprotein complexes. Using a chimeric reporter, polypyrimidine tract-binding protein (PTB) was found to bind the HIF-1 alpha 3'UTR, while HuR associated principally with the 5'UTR. Lowering PTB expression or HuR expression using RNA interference reduced HIF-1 alpha translation and expression levels but not HIF-1 alpha mRNA abundance. Conversely, HIF-1 alpha expression and translation in response to CoCl2 were markedly elevated after HuR overexpression. We propose that HuR and PTB jointly upregulate HIF-1 alpha translation in response to CoCl2.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据