Selective inhibition of rRNA transcription downregulates E2F-1: a new p53-independent mechanism linking cell growth to cell proliferation

• DOI: 10.1242/jcs.086074
• Publication Date: 2011-08-30T16:48:29Z
• Authors: Giulio Donati; Elisa Brighenti; Manuela Vici; Giuliano Mazzini; Davide Treré; Lorenzo Montanaro; Massimo Derenzini
• Keywords: ribosome biogenesis; E2F; Transcription

The tumour suppressor p53 negatively controls cell cycle progression in response to perturbed ribosome biogenesis mammalian cells, thus coordinating growth with proliferation. Unlike is not involved the control of proliferation yeasts and flies. We investigated whether a p53-independent mechanism inadequate rate also present cells. studied effect specific inhibition rRNA synthesis on human cancer lines using small-interfering RNA procedure silence POLR1A gene, which encodes catalytic subunit polymerase I. found that interference inhibited hindered cells inactivated p53, as consequence downregulation transcription factor E2F-1. Downregulation E2F-1 was due release ribosomal protein L11, E2F-1-stabilising function E3 ubiquitin ligase MDM2. These results demonstrated existence links suggested selective targeting I machinery might be advisable hinder p53-deficient