The Promyelocytic Leukaemia gene product PML interacts with Myc and influences the expression of Myc target genes

Cairo, Stefano (2004). The Promyelocytic Leukaemia gene product PML interacts with Myc and influences the expression of Myc target genes. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000fa05

Abstract

c-myc is a well-known proto-oncogene encoding a transcription factor that needs to be tightly regulated in order to preserve cell homeostasis. The Promyelocytic Leukaemia gene product PML plays an important role in cell growth and survival, and resides in discrete sub-nuclear structures called Nuclear Bodies (NB). PML is largely involved in gene regulation via recruitment of several transcription factors and co factors to the NB. In this report, I show that Myc partially localizes to the NB and physically interacts with PML, and I demonstrate that PML over-expression affects Myc-mediated transcription of a reporter gene. Comparative analysis of the expression of 40 Myc target genes and of Myc binding to their regulatory regions in wild type and PML knockout mouse embryo fibroblasts was performed. The data show that if PML is absent, although Myc binding to the DNA regulatory sequences is unchanged, the expression profile of several Myc target genes is altered. As deregulation of both activated and repressed Myc target genes occurs, I propose that PML influences Myc transcriptional activity through a mechanism that involves the control of Myc post-translational modifications.

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