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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Rep 2014 ; 8 (5): 1347-53 Nephropedia Template TP
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BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues #MMPMID25176652
Muthalagu N; Junttila M; Wiese KE; Wolf E; Morton J; Bauer B; Evan GI; Eilers M; Murphy DJ
Cell Rep 2014[Sep]; 8 (5): 1347-53 PMID25176652show ga
MYC is one of the most frequently overexpressed oncogenes in human cancer and even modestly deregulated MYC can initiate ectopic proliferation in many post-mitotic 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 pro-apoptotic BH3 proteins NOXA and PUMA, while 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.