Tristetraprolin regulates the stability of HIF-1α mRNA during prolonged hypoxia
Tristetraprolin regulates the stability of HIF-1α mRNA during prolonged hypoxia
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DOI：
10.1016/j.bbrc.2009.11.174
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Park, Kyung Chan
中科院分区：
文献类型：
--
作者：
Kim, Tae Woo;Yim, Sujin;Park, Kyung Chan
缺氧诱导因子-1（Hypoxia-inducible factor-1，HIF-1）是一种参与肿瘤细胞缺氧适应的转录因子，是导致肿瘤恶性的主要原因。因此，控制HIF-1 α的表达可以帮助治疗癌症。HIF-1 α的表达不仅通过HIF-1 α的改变来精细调节。蛋白质稳定性和mRNA稳定性然而，HIF-1 α调节的分子机制。mRNA的稳定性尚未完全阐明。在此，我们显示了三曲脯氨酸（TTP）蛋白，其mRNA表达水平在大多数肝细胞癌组织中下调。直接结合到HIF-1 α mRNA的3 '-UTR，其含有8个推定的TTP结合基序，富含AU的元件（AUUUA）。下调稳定性。此外。缺氧诱导TTP表达，过表达1713抑制缺氧诱导HIF-1 α蛋白表达。这些数据表明TTP是缺氧期间HIF-1 α表达的调节剂，并且可能在长期缺氧中在细胞适应和凋亡之间的调节中起生理作用。此外，癌细胞可能受益于TTP的下调。其随后增加HIF-1 α表达并帮助癌细胞适应缺氧。(C)2009爱思唯尔公司版权所有
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor involved in the cancer cell adaptation to hypoxia, a leading Cause of tumor malignancy. Thus, control of HIF-1 alpha expression may assist in treatment of cancer The expression of HIF-1 alpha is finely regulated via alterations in not only HIF-1 alpha. protein stability but also mRNA stability However, the molecular mechanisms of regulation of HIF-1 alpha. mRNA stability have not yet been fully elucidated Here, we show that tristetraprolin (TTP) protein, of which the mRNA expression level is downregulated in most of hepatocellular carcinoma tissues. bound directly to the 3'- UTR of HIF-1 alpha mRNA containing eight putative TTP-binding motifs, AU-rich elements (AUUUA). to downregulate stability. Furthermore. TTP expression was induced in hypoxic cells, and overexpression of 1713 repressed the hypoxic induction of HIF-1 alpha protein Taken together. these data Suggest that TTP is a modulator of HIF-1 alpha expression during hypoxia and may play a physiological role in regulation between cellular adaptation and apoptosis in prolonged hypoxia In addition, cancer cells may benefit from the downregulation of TTP. which subsequently increases HIF-1 alpha expression and assists with the adaptation of cancer cells to hypoxia. (C) 2009 Elsevier Inc All rights reserved