ABSTRACT The BMI1 polycomb protein regulates self-renewal, proliferation and survival of cancer-initiating cells essentially through epigenetic repression of the _CDKN2A_ tumor suppressor

locus. We demonstrate here for the first time that BMI1 also prevents autophagy in chronic myeloid leukemia (CML) cell lines, to support their proliferation and clonogenic activity. Using

chromatin immunoprecipitation, we identified _CCNG2_/cyclin G2 (CCNG2) as a direct BMI1 target. BMI1 downregulation in CD34+ CML cells by PTC-209 pharmacological treatment or shBMI1

transduction triggered CCNG2 expression and decreased clonogenic activity. Also, ectopic expression of CCNG2 in CD34+ CML cells strongly decreased their clonogenicity. CCNG2 was shown to act

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NONCANONICAL PRC1.1 TARGETS BTG2 TO RETAIN CYCLIN GENE EXPRESSION AND CELL GROWTH IN NEUROBLASTOMA Article Open access 03 June

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3626–3636. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We are grateful to Malek Djabali (UMR5088 CNRS, Toulouse, France) for helpful discussion during early phases of

the project; Hans Clevers (Hubrecht Laboratory, Utrecht, The Netherlands) for the kind gift of the pTER vector; Agnès Loubat for help in cell cycle analysis; Jan Jacob Schuringa (University

Medical Center Groningen, Hematology, Groningen, The Netherlands) for the kind gift of the shBMI1 lentiviral constructs; Patrick Auberger, Arnaud Jacquel and Sandrine Obba for helpful

discussion concerning autophagy; Catherine Frelin for critical review of the manuscript. We thank Ms Chimène Morillon and Kevin Lebrigand from the Plateforme Génomique Fonctionnelle (IPMC,

Sophia Antipolis, France) for Affymetrix analysis assistance and Dr Bernard Mari for help with transcriptomic analyses. We acknowledge the C3M imaging core facility (Microscopy and Imaging

Platform Côte d'Azur) and the C3M animal room facility. The C3M is supported institutional grants from INSERM. LM is supported by a grant from the French Ministry of Research and a 4th

year PhD grant from the Société Française d’Hématologie (SFH). ACCESSION NUMBER Gene profiling was performed on inducible shBmi1-K562 cells incubated or not with doxycycline (1μg/ml) for 96h

using HG-U133 Plus2 Affymetrix Arrays. AUTHOR INFORMATION Author notes * D Mary and J-F Peyron: These authors share senior coauthorship. AUTHORS AND AFFILIATIONS * INSERM, UMR1065 Centre

Méditerranéen de Médecine Moléculaire C3M, Nice, France L Mourgues, V Imbert, M Nebout, P Colosetti, Z Neffati, P Lagadec, E Verhoeyen, D Mary & J-F Peyron * Equipe Inflammation, Cancer,

Cancer Stem Cells, Nice, France L Mourgues, V Imbert, M Nebout, Z Neffati, P Lagadec, D Mary & J-F Peyron * Université de Nice-Sophia Antipolis, UFR Médecine, Nice, France L Mourgues, V

Imbert, M Nebout, P Colosetti, Z Neffati, P Lagadec, L Legros, N Rochet, D Mary & J-F Peyron * Equipe Cell Death, Differentiation and Cancer, Nice, France P Colosetti & E Verhoeyen

* Equipe Metabolic control of Cell Death in Cancer, Nice, France E Verhoeyen * Department of Biology, York University, Toronto, ON, Canada C Peng * CRCM, U1068, INSERM, Marseille, France E

Duprez * Service d'Hématologie Clinique, Hôpital Archet 1, Nice, France L Legros * Institut de Biologie Valrose (iBV), UMR CNRS 7277-UMR INSERM 1091, Nice, France L Legros & N

Rochet * CNRS, UMR5386, INSERM, U1052, Lyon, France V Maguer-Satta * Service d’Hématologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France F-E Nicolini Authors *

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protein represses cyclin G2-induced autophagy to support proliferation in chronic myeloid leukemia cells. _Leukemia_ 29, 1993–2002 (2015). https://doi.org/10.1038/leu.2015.112 Download

citation * Received: 08 September 2014 * Revised: 27 March 2015 * Accepted: 30 March 2015 * Published: 30 April 2015 * Issue Date: October 2015 * DOI: https://doi.org/10.1038/leu.2015.112

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