Mnt modulates Myc-driven lymphomagenesis
Kirsteen J Campbell, Cassandra J Vandenberg, Natasha S Anstee, Peter J Hurlin, Suzanne Cory
CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2017
The transcriptional represser Mnt is a functional antagonist of the proto-oncoprotein Myc. Both Mnt and Myc utilise Max as an obligate partner for DNA binding, and Myc/Max and Mnt/Max complexes compete for occupancy at E-box DNA sequences in promoter regions. We have previously shown in transgenic mouse models that the phenotype and kinetics of onset of haemopoietic tumours varies with the level of Myc expression. We reasoned that a decrease in the level of Mnt would increase the functional level of Myc and accelerate Myc-driven tumorigenesis. We tested the impact of reduced Mnt in three models of myc transgenic mice and in p53+/- mice. To our surprise, mnt heterozygosity actually slowed Myc..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by National Cancer Institute
Awarded by NATIONAL CANCER INSTITUTE
We thank our colleagues JM Adams, A Strasser, C Scott and P Bouillet for useful discussions; ML Bath for performing in vitro fertilisations; B Helbert, K Mackwell and C Young for genotyping; M Robati for technical assistance; K Hughes, C D'Alessandro and G Siciliano for mouse husbandry, WEHI cytometry and histology services; and L Whitehead for imaging analysis. This work was supported by postdoctoral fellowships from EMBO and the Human Frontier in Science Program (to KJC); a PhD fellowship from Leukaemia Foundation of Australia (to NSA); research grants from National Health and Medical Research Council (NHMRC) (program grant 461221) and National Cancer Institute (CA43540); and operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS.