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Physical and functional interaction of the p14ARF tumor suppressor with ribosomes

Item Type:Article
Title:Physical and functional interaction of the p14ARF tumor suppressor with ribosomes
Creators Name:Rizos, H., McKenzie, H.A., Ayub, A.L., Woodruff, S., Becker, T.M., Scurr, L.L., Stahl, J. and Kefford, R.F.
Abstract:Alterations in the p14(ARF) tumor suppressor are frequent in many human cancers and are associated with susceptibility to melanoma, pancreatic cancer, and nervous system tumors. In addition to its p53-regulatory functions, p14(ARF) has been shown to influence ribosome biogenesis and to regulate the endoribonuclease B23, but there remains considerable controversy about its nucleolar role. We sought to clarify the activities of p14(ARF) by studying its interaction with ribosomes. We show that p14(ARF) and B23 interact within the nucleolar 60 S preribosomal particle and that this interaction does not require rRNA. In contrast to previous reports, we found that expression of p14(ARF) does not significantly alter ribosome biogenesis but inhibits polysome formation and protein translation in vivo. These results suggest a ribosome-dependent p14(ARF) pathway that regulates cell growth and thus complements p53-dependent p14(ARF) functions.
Keywords:Cell Cycle, Cell Division, Gene Expression, Neoplasm Proteins, Neoplasm RNA, Neoplasms, Polyribosomes, Protein Biosynthesis, Recombinant Proteins, Ribosomal RNA, Ribosomes, Tumor Cell Line, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:38080-38088
Date:8 December 2006
Official Publication:https://doi.org/10.1074/jbc.M609405200
PubMed:View item in PubMed

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