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

Muthalagu, N., Junttila, M. R., Wiese, K. E., Wolf, E., Morton, J. , Bauer, B., Evan, G. I., Eilers, M. and Murphy, D. J. (2014) BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues. Cell Reports, 8(5), pp. 1347-1353. (doi: 10.1016/j.celrep.2014.07.057)

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Abstract

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 of BH3 proteins, especially BIM. 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 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel and Morton, Professor Jen
Authors: Muthalagu, N., Junttila, M. R., Wiese, K. E., Wolf, E., Morton, J., Bauer, B., Evan, G. I., Eilers, M., and Murphy, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Reports
Publisher:Elsevier
ISSN:2211-1247
Published Online:28 August 2014
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Cell Reports
Publisher Policy:Reproduced under a Creative Commons License

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