APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process

Carlo Vascotto, Damiano Fantini, Milena Romanello, Laura Cesaratto, Marta Deganuto, Antonio Leonardi, J. Pablo Radicella, Mark Kelley, Chiara D'Ambrosio, Andrea Scaloni, Franco Quadrifoglio, Gianluca Tell

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

APEl/Ref-1 (hereafter, APE1), a DNA repair enzyme and a transcriptional coactivator, is a vital protein in mammals. Its role in controlling cell growth and the molecular mechanisms that fine-tune its different cellular functions are still not known. By an unbiased proteomic approach, we have identified and characterized several novel APE1 partners which, unexpectedly, include a number of proteins involved in ribosome biogenesis and RNA processing. In particular, a novel interaction between nucleophosmin (NPM1) and APE1 was characterized. We observed that the 33 N-terminal residues of APE1 are required for stable interaction with the NPM1 oligomerization domain. As a consequence of the interaction with NPM1 and RNA, APE1 is localized within the nucleolus and this localization depends on cell cycle and active rRNA transcription. NPM1 stimulates APE1 endonuclease activity on abasic double-stranded DNA (dsDNA) but decreases APE1 endonuclease activity on abasic single-stranded RNA (ssRNA) by masking the N-terminal region of APE1 required for stable RNA binding. In APEl-knocked-down cells, pre-rRNA synthesis and rRNA processing were not affected but inability to remove 8-hydroxyguanine-containing rRNA upon oxidative stress, impaired translation, lower intracellular protein content, and decreased cell growth rate were found. Our data demonstrate that APE1 affects cell growth by directly acting on RNA quality control mechanisms, thus affecting gene expression through posttranscriptional mechanisms.

Original languageEnglish
Pages (from-to)1834-1854
Number of pages21
JournalMolecular and Cellular Biology
Volume29
Issue number7
DOIs
StatePublished - Apr 2009

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Quality Control
RNA
Endonucleases
Growth
Proteins
RNA Precursors
Ribosomes
Proteomics
Mammals
Cell Cycle
Oxidative Stress
Gene Expression
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Vascotto, C., Fantini, D., Romanello, M., Cesaratto, L., Deganuto, M., Leonardi, A., ... Tell, G. (2009). APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Molecular and Cellular Biology, 29(7), 1834-1854. https://doi.org/10.1128/MCB.01337-08

APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. / Vascotto, Carlo; Fantini, Damiano; Romanello, Milena; Cesaratto, Laura; Deganuto, Marta; Leonardi, Antonio; Radicella, J. Pablo; Kelley, Mark; D'Ambrosio, Chiara; Scaloni, Andrea; Quadrifoglio, Franco; Tell, Gianluca.

In: Molecular and Cellular Biology, Vol. 29, No. 7, 04.2009, p. 1834-1854.

Research output: Contribution to journalArticle

Vascotto, C, Fantini, D, Romanello, M, Cesaratto, L, Deganuto, M, Leonardi, A, Radicella, JP, Kelley, M, D'Ambrosio, C, Scaloni, A, Quadrifoglio, F & Tell, G 2009, 'APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process', Molecular and Cellular Biology, vol. 29, no. 7, pp. 1834-1854. https://doi.org/10.1128/MCB.01337-08
Vascotto, Carlo ; Fantini, Damiano ; Romanello, Milena ; Cesaratto, Laura ; Deganuto, Marta ; Leonardi, Antonio ; Radicella, J. Pablo ; Kelley, Mark ; D'Ambrosio, Chiara ; Scaloni, Andrea ; Quadrifoglio, Franco ; Tell, Gianluca. / APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 7. pp. 1834-1854.
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