TY  - JOUR
A1  - Muthalagu, Nathiya
A1  - Junttila, Melissa R.
A1  - Wiese, Kathrin E.
A1  - Wolf, Elmar
A1  - Morton, Jennifer
A1  - Bauer, Barbara
A1  - Evan, Gerard I.
A1  - Eilers, Martin
A1  - Murphy, Daniel J.
T1  - BIM Is the Primary Mediator of MYC-Induced Apoptosis in Multiple Solid Tissues
JF  - Cell Reports
N2  - 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.
KW  - ARF tumor-suppressor induced lymphomagenes
KW  - BCL-X-L P53
KW  - C-MYC PUMA
KW  - in-vivo expression
KW  - cell-cycle arrest cancer therapy
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115370
VL  - 8
IS  - 5
ER  -