The p14ARF Tumor Suppressor Protein Facilitates Nucleolar Sequestration of Hypoxia-inducible Factor-1α (HIF-1α) and Inhibits HIF-1-mediated Transcription

Karoly Fatyol, Aladar A. Szalay

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Oncogenic alterations can influence tumor cell survival partly by affecting the activity of the hypoxia-inducible factor-1 (HIF-1) transcription factor. The α 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 α 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 p14ARF.

Original languageEnglish
Pages (from-to)28421-28429
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number30
DOIs
Publication statusPublished - Jul 27 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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