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• W2273708684 abstract "// Laura Di Magno 3 , Alessio Basile 1 , Sonia Coni 1 , Simona Manni 1 , Giulia Sdruscia 3 , Davide D’Amico 1 , Laura Antonucci 1 , Paola Infante 3 , Enrico De Smaele 2 , Danilo Cucchi 2 , Elisabetta Ferretti 2 , Lucia Di Marcotullio 1, 3, 4 , Isabella Screpanti 1, 3, 4 , Gianluca Canettieri 1, 4 1 Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy 2 Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy 3 Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, 00161 Roma, Italy 4 Istituto Pasteur, Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00161 Rome, Italy Correspondence to: Gianluca Canettieri, e-mail: gianluca.canettieri@uniroma1.it Keywords: Hedgehog, AMPK, Gli1, cancer metabolism, phosphorylation Received: August 18, 2015      Accepted: January 12, 2016      Published: January 29, 2016 ABSTRACT Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species. Studies with selective agonists and genetic deletion have revealed that AMPK activation inhibits canonical Hh signaling in human, but not in mouse cells. Indeed we show that AMPK phosphorylates Gli1 at the unique residue Ser408, which is conserved only in primates but not in other species. Once phosphorylated, Gli1 is targeted for proteasomal degradation. Notably, we show that selective AMPK activation inhibits Gli1-driven proliferation and that this effect is linked to Ser408 phosphorylation, which represents a key metabolic checkpoint for Hh signaling. Collectively, this data unveil a novel mechanism of inhibition of Gli1 function, which is exclusive for human cells and may be exploited for the treatment of Medulloblastoma or other Gli1 driven tumors." @default.
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• W2273708684 date "2016-01-29" @default.
• W2273708684 modified "2023-10-14" @default.
• W2273708684 title "The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint" @default.
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• W2273708684 doi "https://doi.org/10.18632/oncotarget.7070" @default.
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