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Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF

Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF Downloaded from genesdev.cshlp.org on November 18, 2021 - Published by Cold Spring Harbor Laboratory Press Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF 1,3 2,3 1 1 2 Jacqueline J.L. Jacobs, Blanca Scheijen, Jan-Willem Voncken, Karin Kieboom, Anton Berns, 1,4 and Maarten van Lohuizen 1 2 Division of Molecular Carcinogenesis and Division of Molecular Genetics and Centre of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands The bmi-1 and myc oncogenes collaborate strongly in murine lymphomagenesis, but the basis for this collaboration was not understood. We recently identified the ink4a–ARF tumor suppressor locus as a critical downstream target of the Polycomb-group transcriptional repressor Bmi-1. Others have shown that part of Myc’s ability to induce apoptosis depends on induction of p19arf. Here we demonstrate that down-regulation of ink4a–ARF by Bmi-1 underlies its ability to cooperate with Myc in tumorigenesis. Heterozygosity for bmi-1 inhibits lymphomagenesis in Eμ–myc mice by enhancing c-Myc-induced apoptosis. We observe increased −/− apoptosis in bmi-1 lymphoid organs, which can be rescued by deletion of ink4a–ARF or overexpression of bcl2. Furthermore, Bmi-1 collaborates with Myc in enhancing proliferation and transformation of primary embryo fibroblasts (MEFs) in an ink4a–ARF dependent manner, by http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genes & Development Unpaywall

Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF

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Unpaywall
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0890-9369
DOI
10.1101/gad.13.20.2678
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Abstract

Downloaded from genesdev.cshlp.org on November 18, 2021 - Published by Cold Spring Harbor Laboratory Press Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF 1,3 2,3 1 1 2 Jacqueline J.L. Jacobs, Blanca Scheijen, Jan-Willem Voncken, Karin Kieboom, Anton Berns, 1,4 and Maarten van Lohuizen 1 2 Division of Molecular Carcinogenesis and Division of Molecular Genetics and Centre of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands The bmi-1 and myc oncogenes collaborate strongly in murine lymphomagenesis, but the basis for this collaboration was not understood. We recently identified the ink4a–ARF tumor suppressor locus as a critical downstream target of the Polycomb-group transcriptional repressor Bmi-1. Others have shown that part of Myc’s ability to induce apoptosis depends on induction of p19arf. Here we demonstrate that down-regulation of ink4a–ARF by Bmi-1 underlies its ability to cooperate with Myc in tumorigenesis. Heterozygosity for bmi-1 inhibits lymphomagenesis in Eμ–myc mice by enhancing c-Myc-induced apoptosis. We observe increased −/− apoptosis in bmi-1 lymphoid organs, which can be rescued by deletion of ink4a–ARF or overexpression of bcl2. Furthermore, Bmi-1 collaborates with Myc in enhancing proliferation and transformation of primary embryo fibroblasts (MEFs) in an ink4a–ARF dependent manner, by

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Genes & Development – Unpaywall

Published: Oct 15, 1999

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