Surveillance of ribosome assembly plays an important role in the regulation of cell growth and defects in ribosome biogenesis can lead to cell cycle arrest or apoptosis. Mounting evidences show that several ribosomal proteins may be involved in this regulation through extraribosomal function. A main outcome of the impairment of the ribosome synthesis is the nucleolus destruction and the p53 stabilization through the inhibitory interaction between some ribosomal proteins and MDM2. The effects of p53 activation are mainly mediated by upregulation of p21 which promotes cell cycle arrest or apoptosis, depending on the cellular context. In addition to p53, several other proteins are able to activate p21 expression. It has been demonstrated that various protein factors involved in ribosome biogenesis such as nucleophosmin (NPM) can regulate p21 expression p53-independently at transcriptional and post-translational levels. In a previous study, we have reported a direct protein-protein interaction between NPM and the ribosomal protein rpL3, required for the autoregulatory circuit of the rpL3 expression. We wondered whether this interaction could occur also in another context and whether rpL3 could be involved in the regulation of p21 expression. In order to verify this hypothesis, we first analyzed changes in p21 protein levels in p53-null Calu-6 cells upon alteration of rpL3 production. We performed transient transfection experiments of a construct encoding for the recombinant protein HA-rpL3 in the aforementioned cell lines. We observed that the enforced expression of the HA-rpL3 protein resulted in a dose-dependent increasing of p21 protein amount. In addition, the rpL3-mediated p21 upregulation was associated with cell cycle arrest in Calu-6 cells. The results of these experiments will be discussed.

A novel extraribosomal function of human rpL3 involves antitumoral activity in Calu-6 cells through p21-dependent mitochondrial apoptosis / Davide, Esposito; Russo, Annapina; Morena, Catillo; Enrico, Mazzarella; Concetta, Pietropaolo; Russo, Giulia. - (2012). (Intervento presentato al convegno ABCD Meeting Cell Stress: Survival and Apoptosis tenutosi a Firenze nel 18/05/2012).

A novel extraribosomal function of human rpL3 involves antitumoral activity in Calu-6 cells through p21-dependent mitochondrial apoptosis.

RUSSO, ANNAPINA;RUSSO, GIULIA
2012

Abstract

Surveillance of ribosome assembly plays an important role in the regulation of cell growth and defects in ribosome biogenesis can lead to cell cycle arrest or apoptosis. Mounting evidences show that several ribosomal proteins may be involved in this regulation through extraribosomal function. A main outcome of the impairment of the ribosome synthesis is the nucleolus destruction and the p53 stabilization through the inhibitory interaction between some ribosomal proteins and MDM2. The effects of p53 activation are mainly mediated by upregulation of p21 which promotes cell cycle arrest or apoptosis, depending on the cellular context. In addition to p53, several other proteins are able to activate p21 expression. It has been demonstrated that various protein factors involved in ribosome biogenesis such as nucleophosmin (NPM) can regulate p21 expression p53-independently at transcriptional and post-translational levels. In a previous study, we have reported a direct protein-protein interaction between NPM and the ribosomal protein rpL3, required for the autoregulatory circuit of the rpL3 expression. We wondered whether this interaction could occur also in another context and whether rpL3 could be involved in the regulation of p21 expression. In order to verify this hypothesis, we first analyzed changes in p21 protein levels in p53-null Calu-6 cells upon alteration of rpL3 production. We performed transient transfection experiments of a construct encoding for the recombinant protein HA-rpL3 in the aforementioned cell lines. We observed that the enforced expression of the HA-rpL3 protein resulted in a dose-dependent increasing of p21 protein amount. In addition, the rpL3-mediated p21 upregulation was associated with cell cycle arrest in Calu-6 cells. The results of these experiments will be discussed.
2012
A novel extraribosomal function of human rpL3 involves antitumoral activity in Calu-6 cells through p21-dependent mitochondrial apoptosis / Davide, Esposito; Russo, Annapina; Morena, Catillo; Enrico, Mazzarella; Concetta, Pietropaolo; Russo, Giulia. - (2012). (Intervento presentato al convegno ABCD Meeting Cell Stress: Survival and Apoptosis tenutosi a Firenze nel 18/05/2012).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/596973
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