The nucleolar protein nucleophosmin is essential for autophagy induced by inhibiting Pol I transcription.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Transcription, Genetic*; Autophagy/*genetics ; Nuclear Proteins/*genetics ; RNA Polymerase I/*genetics; Cell Nucleolus/genetics ; Humans ; MCF-7 Cells ; Nuclear Proteins/antagonists & inhibitors ; Nucleolus Organizer Region/genetics ; Nucleophosmin ; RNA Polymerase I/antagonists & inhibitors ; RNA, Small Interfering

Various cellular stresses activate autophagy, which is involved in lysosomal degradation of cytoplasmic materials for maintaining nutrient homeostasis and eliminating harmful components. Here, we show that RNA polymerase I (Pol I) transcription inhibition induces nucleolar disruption and autophagy. Treatment with autophagy inhibitors or siRNA specific for autophagy-related (ATG) proteins inhibited autophagy but not nucleolar disruption induced by Pol I transcription inhibition, which suggested that nucleolar disruption was upstream of autophagy. Furthermore, treatment with siRNA specific for nucleolar protein nucleophosmin (NPM) inhibited this type of autophagy. This showed that NPM was involved in autophagy when the nucleolus was disrupted by Pol I inhibition. In contrast, NPM was not required for canonical autophagy induced by nutrient starvation, as it was not accompanied by nucleolar disruption. Thus, our results revealed that, in addition to canonical autophagy, there may be NPM-dependent autophagy associated with nucleolar disruption.

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0 (NPM1 protein, human)
0 (Nuclear Proteins)
0 (RNA, Small Interfering)
117896-08-9 (Nucleophosmin)
EC 2.7.7.6 (RNA Polymerase I)

Date Created: 20150311 Date Completed: 20151209 Latest Revision: 20230815

20250114

PMC4354046

10.1038/srep08903

25754892