Recent evidence showed that a variety of DNA damaging agents including 5-FU and L-OHP impairs ribosomal biogenesis activating a ribosomal stress pathway. Here, that ribosomal stress induced by 5-FU and L-OHP is associated to up-regulation of rpL3 and its accumulation as ribosome-free form. We show that rpL3 participates in the cell response to chemotherapy acting as a critical regulator of cell cycle, apoptosis and DNA repair, by modulating p21 expression. Moreover, we demonstrate that rpL3 is able to control DNA repair also independently from p21 status of cell. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of 5-FU and L-OH indicating that the loss of rpL3 makes chemotherapy drugs ineffective. Taking together our results shed light on 5-FU and L-OHP mechanism of action and contribute to more effective clinical use of these drugs in cancer therapy.

Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP / Esposito, Davide; Crescenzi, Elvira; Sagar, Vinay; Loreni, Fabrizio; Russo, Annapina; Russo, Giulia. - In: ONCOTARGET. - ISSN 1949-2553. - 5:22(2014), pp. 11737-11751. [10.18632/oncotarget.2591]

Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP

CRESCENZI, ELVIRA;RUSSO, ANNAPINA;RUSSO, GIULIA
2014

Abstract

Recent evidence showed that a variety of DNA damaging agents including 5-FU and L-OHP impairs ribosomal biogenesis activating a ribosomal stress pathway. Here, that ribosomal stress induced by 5-FU and L-OHP is associated to up-regulation of rpL3 and its accumulation as ribosome-free form. We show that rpL3 participates in the cell response to chemotherapy acting as a critical regulator of cell cycle, apoptosis and DNA repair, by modulating p21 expression. Moreover, we demonstrate that rpL3 is able to control DNA repair also independently from p21 status of cell. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of 5-FU and L-OH indicating that the loss of rpL3 makes chemotherapy drugs ineffective. Taking together our results shed light on 5-FU and L-OHP mechanism of action and contribute to more effective clinical use of these drugs in cancer therapy.
2014
Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP / Esposito, Davide; Crescenzi, Elvira; Sagar, Vinay; Loreni, Fabrizio; Russo, Annapina; Russo, Giulia. - In: ONCOTARGET. - ISSN 1949-2553. - 5:22(2014), pp. 11737-11751. [10.18632/oncotarget.2591]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/617643
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