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Published on: May 1, 2020
Physical and functional interaction of the p14ARF tumor suppressor with ribosomes
Helen Rizos1, Heather A McKenzie, Ana Luisa Ayub
1Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales 2145, Australia. helen_rizos@wmi.usyd.edu.au
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.
Insights
The tumor suppressor p14ARF interacts with ribosomes, impacting protein translation. This suggests a new pathway for p14ARF in regulating cell growth, complementing its known p53 functions.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- p14ARF is a tumor suppressor frequently altered in human cancers.
- Its role in the nucleolus and ribosome biogenesis is controversial.
- p14ARF is known to regulate p53 and the protein B23.
Purpose of the Study:
- To clarify the nucleolar functions of p14ARF.
- To investigate the interaction of p14ARF with ribosomes.
- To determine the effect of p14ARF on ribosome biogenesis and protein translation.
Main Methods:
- Studying the interaction between p14ARF and ribosomes.
- Analyzing the effect of p14ARF expression on polysome formation and protein translation in vivo.
- Investigating the interaction of p14ARF with the endoribonuclease B23 within the nucleolar 60 S preribosomal particle.
Main Results:
- p14ARF and B23 interact within the 60 S preribosomal particle.
- This interaction does not require rRNA.
- p14ARF expression inhibits polysome formation and protein translation in vivo, without significantly altering ribosome biogenesis.
Conclusions:
- p14ARF has a ribosome-dependent pathway that regulates cell growth.
- This pathway complements the known p53-dependent functions of p14ARF.
- p14ARF's role in regulating protein translation provides new insights into its tumor suppressor activities.
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