The p14ARF tumor suppressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1α (HIF-1α) and inhibits HIF-1-mediated transcription
The p14ARF tumor suppressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1α (HIF-1α) and inhibits HIF-1-mediated transcription
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DOI：
10.1074/jbc.m102847200
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发表时间：
2001-07-27
影响因子：
4.8
通讯作者：
Szalay, AA
中科院分区：
文献类型：
--
作者：
Fatyol, K;Szalay, AA
致癌性改变可以部分地通过影响缺氧诱导因子-1（HIF-1）转录因子的活性来影响肿瘤细胞存活。HIF-1的α亚基在晚期肿瘤中频繁过表达，这被认为有助于肿瘤细胞适应缺氧。在这里，我们表明，一个重要的肿瘤抑制蛋白，p14（ARF）（替代阅读框产品的INK 4A基因座）可以直接抑制HIF-1的转录活性，通过隔离其α亚基到核仁。这种相互作用既不需要p53也不需要HDM 2。这是描述p14（ARF）与除HDM 2之外的蛋白质的相互作用的第一个报告之一，其可以定义p14（ARF）的p53非依赖性肿瘤抑制活性。
Oncogenic alterations can influence tumor cell survival partly by affecting the activity of the hypoxia-inducible factor-1 (HIF-1) transcription factor. The a subunit of HIF-1 was found to be frequently overexpressed in advanced tumors, which was proposed to help the adaptation of tumor cells to hypoxia. Here we show that an important tumor suppressor protein, p14(ARF) (alternative reading frame product of the INK4A locus) can directly inhibit the transcriptional activity of HIF-1 by sequestering its alpha subunit into the nucleolus. The interaction requires neither p53 nor HDM2. This is one of the first reports that describe the interaction of p14(ARF) with a protein besides HDM2, which may define a p53-independent tumor suppressor activity for p14(ARF).