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BIM Is the Primary Mediator of MYC-Induced Apoptosis in Multiple Solid Tissues

Please always quote using this URN: urn:nbn:de:bvb:20-opus-115370
  • 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 aMYC 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.show moreshow less

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Metadaten
Author: Nathiya Muthalagu, Melissa R. Junttila, Kathrin E. Wiese, Elmar Wolf, Jennifer Morton, Barbara Bauer, Gerard I. Evan, Martin Eilers, Daniel J. Murphy
URN:urn:nbn:de:bvb:20-opus-115370
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Cell Reports
Year of Completion:2014
Volume:8
Issue:5
Pagenumber:1347-1353
Source:Cell Reports 8, 1347–1353. DOI 10.1016/j.celrep.2014.07.057
DOI:https://doi.org/10.1016/j.celrep.2014.07.057
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ARF tumor-suppressor induced lymphomagenes; BCL-X-L P53; C-MYC PUMA; cell-cycle arrest cancer therapy; in-vivo expression
Release Date:2015/07/14
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung