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Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53.
Russo, Annapina; Pagliara, Valentina; Albano, Francesco; Esposito, Davide; Sagar, Vinay; Loreni, Fabrizio; Irace, Carlo; Santamaria, Rita; Russo, Giulia.
Afiliación
  • Russo A; a Department of Pharmacia , University of Naples "Federico II," ; Naples , Italy.
  • Pagliara V; a Department of Pharmacia , University of Naples "Federico II," ; Naples , Italy.
  • Albano F; a Department of Pharmacia , University of Naples "Federico II," ; Naples , Italy.
  • Esposito D; b Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II," Naples , Italy.
  • Sagar V; c Department of Oncological Sciences , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
  • Loreni F; d Department of Biology , University of Rome "Tor Vergata," Rome , Italy.
  • Irace C; d Department of Biology , University of Rome "Tor Vergata," Rome , Italy.
  • Santamaria R; a Department of Pharmacia , University of Naples "Federico II," ; Naples , Italy.
  • Russo G; a Department of Pharmacia , University of Naples "Federico II," ; Naples , Italy.
Cell Cycle ; 15(1): 41-51, 2016.
Article en En | MEDLINE | ID: mdl-26636733
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Estrés Fisiológico / Nucléolo Celular / Proteína p53 Supresora de Tumor / Dactinomicina Límite: Humans Idioma: En Revista: Cell Cycle Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Ribosómicas / Estrés Fisiológico / Nucléolo Celular / Proteína p53 Supresora de Tumor / Dactinomicina Límite: Humans Idioma: En Revista: Cell Cycle Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos