BIM Is the Primary Mediator of MYC-Induced Apoptosis in Multiple Solid Tissues
| Autor: | Gerard I. Evan, Daniel J. Murphy, Martin Eilers, Katrin E. Wiese, Nathiya Muthalagu, B. Bauer, Elmar Wolf, Melissa R. Junttila, Jennifer P. Morton |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cell type
Antineoplastic Agents Apoptosis Article General Biochemistry Genetics and Molecular Biology Proto-Oncogene Proteins c-myc Islets of Langerhans Mice Mediator In vivo Proto-Oncogene Proteins Puma hemic and lymphatic diseases medicine Animals Doxorubicin ddc:610 Intestinal Mucosa lcsh:QH301-705.5 Cyclin-Dependent Kinase Inhibitor p16 Inhibitor of apoptosis domain Bcl-2-Like Protein 11 biology Tumor Suppressor Proteins Membrane Proteins biology.organism_classification In vitro Intestines Mice Inbred C57BL Liver lcsh:Biology (General) Cancer research biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins medicine.drug |
| Zdroj: | Cell Reports, Vol 8, Iss 5, Pp 1347-1353 (2014) |
| ISSN: | 2211-1247 |
| Popis: | SummaryMYC 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. |
| Databáze: | OpenAIRE |
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