Several experimental strategies in the treatment of cancer include drug alteration of cell cycle regulatory pathways as a useful strategy. Extra-ribosomal functions of human ribosomal protein L3 (uL3) may affect DNA repair, cell cycle arrest and apoptosis. In the present study, we demonstrated that uL3 is required for the activation of G1/S transition genes. Luciferase assays established that uL3 negatively regulates the activity of E2F1 promoter. Induced ribosome-free uL3 reduces Cyclin D1 mRNA and protein levels. Using protein/protein immunoprecipitation methods, we demonstrated that uL3 physically interacts with PARP-1 affecting E2F1 transcriptional activity. Our findings led to the identification of a new pathway mediated by uL3 involving E2F1 and Cyclin D1 in the regulation of cell cycle progression.

Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress / Pecoraro, Annalisa; Carotenuto, Pietro; Russo, Giulia; Russo, Annapina. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 9:1(2019), p. 15431. [10.1038/s41598-019-51723-7]

Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress

Pecoraro Annalisa
Primo
Investigation
;
Carotenuto Pietro;Russo Giulia
Penultimo
Conceptualization
;
Russo Annapina
Ultimo
Conceptualization
2019

Abstract

Several experimental strategies in the treatment of cancer include drug alteration of cell cycle regulatory pathways as a useful strategy. Extra-ribosomal functions of human ribosomal protein L3 (uL3) may affect DNA repair, cell cycle arrest and apoptosis. In the present study, we demonstrated that uL3 is required for the activation of G1/S transition genes. Luciferase assays established that uL3 negatively regulates the activity of E2F1 promoter. Induced ribosome-free uL3 reduces Cyclin D1 mRNA and protein levels. Using protein/protein immunoprecipitation methods, we demonstrated that uL3 physically interacts with PARP-1 affecting E2F1 transcriptional activity. Our findings led to the identification of a new pathway mediated by uL3 involving E2F1 and Cyclin D1 in the regulation of cell cycle progression.
2019
Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress / Pecoraro, Annalisa; Carotenuto, Pietro; Russo, Giulia; Russo, Annapina. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 9:1(2019), p. 15431. [10.1038/s41598-019-51723-7]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/774801
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