sirt1 promotes n-myc oncogenesis through a positive feedback loop involving the effects of mkp3 and erk on n-myc protein stabilitysirt1促进n-myc瘤形成通过正反馈循环涉及mkp3和erk n-myc蛋白质稳定性的影响.pdfVIP

SIRT1 Promotes N-Myc Oncogenesis through a Positive Feedback Loop Involving the Effects of MKP3 and ERK on N-Myc Protein Stability 1,2. 1. 3 4 5 Glenn M. Marshall , Pei Y. Liu , Samuele Gherardi , Christopher J. Scarlett , Antonio Bedalov , Ning 1 3 3 1 1 1 1 Xu , Nuncio Iraci , Emanuele Valli , Dora Ling , Wayne Thomas , Margo van Bekkum , Eric Sekyere , 1 1 1 1 1 Kacper Jankowski , Toby Trahair , Karen L. MacKenzie , Michelle Haber , Murray D. Norris , Andrew V. 4 3 1 Biankin , Giovanni Perini , Tao Liu * 1 Children’s Cancer Institute Australia for Medical Research, Randwick, Australia, 2 The Centre for Children’s Cancer and Blood Disorders, Sydney Children’s Hospital, Randwick, Australia, 3 Department of Biology, University of Bologna, Bologna, Italy, 4 Garvan Institute of Medical Research, Darlinghurst, Australia, 5 Fred Hutchinson Cancer Research Centre, University of Washington, Seattle, Washington, United States of America Abstract The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting a low-level to a high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel positive feedback loop whereby N-Myc directly induced the transcription of the class III histone deacetylase SIRT1, wh