The p14ARF tumor suppressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1α (HIF-1α) and inhibits HIF-1-mediated transcription

被引:98
作者
Fatyol, K [1 ]
Szalay, AA [1 ]
机构
[1] Loma Linda Univ, Dept Biochem, Loma Linda, CA 92350 USA
关键词
D O I
10.1074/jbc.M102847200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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).
引用
收藏
页码:28421 / 28429
页数:9
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