Many chemotherapeutic drugs cause nucleolar stress and p53-independent pathways mediating the nucleolar stress response are emerging. Here, we demonstrate that ribosomal stress induced by Actinomycin D (Act D) is associated to the up-regulation of ribosomal protein L3 (rpL3) and its accumulation as ribosome-free form in lung and colon cancer cell lines devoid of p53. Free rpL3 regulates p21 expression at transcriptional and post-translational levels through a molecular mechanism involving extracellular-signal-regulated kinases1/2 (ERK1/2) and mouse double minute-2 homolog (MDM2). Our data reveal that rpL3 participates to cell response acting as a critical regulator of apoptosis and cell migration. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of Act D suggesting that the loss of rpL3 makes chemotherapy drugs ineffective while rpL3 overexpression associates to a strong increase of Act D-mediated inhibition of cell migration. Taking together our results show that the efficacy of Act D chemotherapy depends on rpL3 status revealing new specific targets involved in the molecular pathways activated by Act D in cancers lacking of p53. Hence, the development of treatments aimed at upregulating rpL3 may be beneficial for the treatment of these cancers.
Russo, A., Pagliara, V., Albano, F., Esposito, D., Sagar, V., Loreni, F., et al. (2016). Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53. CELL CYCLE, 15(1), 41-51-51.
|Tipologia:||Articolo su rivista|
|Citazione:||Russo, A., Pagliara, V., Albano, F., Esposito, D., Sagar, V., Loreni, F., et al. (2016). Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53. CELL CYCLE, 15(1), 41-51-51.|
|Settore Scientifico Disciplinare:||Settore BIO/11|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1080/15384101.2015.1120926|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2016|
|Titolo:||Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53|
|Autori:||Russo, A; Pagliara, V; Albano, F; Esposito, D; Sagar, V; Loreni, F; Irace, C; Santamaria, R; Russo, G|
|Appare nelle tipologie:||01 - Articolo su rivista|