Genomics

Dataset Information

300

BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues


ABSTRACT: C-MYC (henceforth MYC) is one of the most frequently overexpressed oncogenes in human cancer and even modestly deregulated MYC expression can initiate ectopic proliferation in many post-mitotic, terminally differentiated cell types in vivo. Metazoan organisms have consequently evolved a number of mechanisms to counteract MYC's oncogenic potential, of which apoptosis is arguably the best understood. However, the mechanisms through which MYC induces apoptosis remains controversial, with some studies implicating p19ARF-mediated stabilization of p53, followed by induction of pro-apoptotic BH3 family member NOXA and PUMA, while others argue for more direct regulation of BH3 proteins, especially BIM. The debate likely stems from the use of different experimental systems, modes of perturbation, and quite possibly different levels of MYC expression. Here, we use a single experimental system to systematically evaluate the roles of p19ARF and BIM during MYC-induced apoptosis, in vitro, in vivo, and in combination with a widely used tumoricidal chemotherapeutic, Doxorubicin. We find a common specific requirement for BIM during MYC-induced apoptosis in multiple settings, which does not extend to the p53-responsive BH3 family member PUMA, and find no evidence of a role for p19ARF during MYC-induced apoptosis in the tissues examined. MYC-ER ChIP-Seq with HC20 anti-ER antibody in MCF10A cells performed on an Illumina IIx Genome Analyzer.

ORGANISM(S): Homo sapiens  

SUBMITTER: Elmar Wolf   Gerard I Evan  Barbara Bauer  Katrin E Wiese  Daniel J Murphy  Nathiya Muthalagu  Martin Eilers  Susanne Walz  Jennifer Morton  Melissa Juntilla 

PROVIDER: E-GEOD-59001 | ArrayExpress | 2015-05-18

SECONDARY ACCESSION(S): GSE59001SRP043969PRJNA254075

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues.

Muthalagu Nathiya N   Junttila Melissa R MR   Wiese Katrin E KE   Wolf Elmar E   Morton Jennifer J   Bauer Barbara B   Evan Gerard I GI   Eilers Martin M   Murphy Daniel J DJ  

Cell reports 20140828 5


MYC is one of the most frequently overexpressed oncogenes in human cancer, and even modestly deregulated MYC can initiate ectopic proliferation in many postmitotic cell types in vivo. Sensitization of cells to apoptosis limits MYC's oncogenic potential. However, the mechanism through which MYC induces apoptosis is controversial. Some studies implicate p19ARF-mediated stabilization of p53, followed by induction of proapoptotic BH3 proteins NOXA and PUMA, whereas others argue for direct regulation  ...[more]

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