Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show?
Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show?
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DOI：
10.1016/j.bbcan.2009.01.001
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发表时间：
2009-04
影响因子：
11.2
通讯作者：
Stanbridge, Eric J.
中科院分区：
文献类型：
--
作者：
Kaluz, Stefan;Kaluzova, Milota;Liao, Shu-Yuan;Lerman, Michael;Stanbridge, Eric J.
缺氧介导的转录激活是由缺氧诱导因子（HIF）通过与缺氧反应因子（HRE）结合介导的。实体肿瘤的缺氧与疾病预后较差有关，可靠的肿瘤缺氧细胞标志物将是一个有价值的诊断标志物和潜在的治疗靶点。在这个类别中，碳酸酐酶IX （CAIX）是最有希望的候选之一。在此，我们对CA9转录调控的相关知识进行了综述。HRE是CA9启动子的中心调控元件，而其他元件仅限于在HRE接收的信号放大中发挥较小的作用。对CA9激活的已知机制的分析揭示了HIF-1通路的突出作用。具有非偶联HIF-1α稳定性和转录活性的实验范式（细胞周围缺氧，蛋白酶体抑制剂）证明CA9表达监测HIF-1的转录活性，而不是HIF-1α的丰度。此外，这些模式可以为体内观察到的一些明显不一致的情况（CAIX+, HIF-1α -）或（CAIX -, HIF-1α+）提供推论。综上所述，现有的数据支持这样的观点，即CA9由于其启动子的独特结构，是HIF-1活性最敏感的内源性传感器之一。
Transcriptional activation by hypoxia is mediated by the hypoxia-inducible factor (HIF) via binding to the hypoxia-responsive element (HRE). Hypoxia in solid tumors associates with poorer outcome of the disease and reliable cellular markers of tumor hypoxia would represent a valuable diagnostic marker and a potential therapeutic target. In this category, carbonic anhydrase IX (CAIX) is one of the most promising candidates. Here, we summarize the knowledge about transcriptional regulation of CA9. The HRE is the central regulatory element in the CA9 promoter, whereas other elements are limited to lesser roles of amplification of signals received at the HRE. The analysis of known mechanisms of activation of CA9 reveals the prominent role of the HIF-1 pathway. Experimental paradigms with uncoupled HIF-1α stability and transcriptional activity (pericellular hypoxia, proteasomal inhibitor) provide evidence that CA9 expression monitors transcriptional activity of HIF-1, rather than the abundance of HIF-1α. Furthermore, these paradigms could provide a corollary to some of the apparently discordant cases (CAIX+, HIF-1α−) or (CAIX−, HIF-1α+) observed in vivo. In conclusion, the existing data support the notion that CA9, due to the unique structure of its promoter, is one of the most sensitive endogenous sensors of HIF-1 activity.
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影响因子：
4.8
作者：
Blagosklonny, MV;An, WG;Neckers, L
通讯作者：
Neckers, L
影响因子：
3.4
作者：
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通讯作者：
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影响因子：
4.1
作者：
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影响因子：
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通讯作者：
Pastorek, J.
影响因子：
3.5
作者：
Bae, Soo-Kyung;Kim, Su-Ryun;Bae, Moon-Kyoung
通讯作者：
Bae, Moon-Kyoung