BCL2 Is a Downstream Effector of MIZ-1 Essential for Blocking c-MYC-induced Apoptosis

An N-Myc truncation analogous to c-Myc-S induces cell proliferation independently of transactivation but dependent on Myc homology box II

“…We found that c-Myc repression of both the Myc promoter and GADD45a was maximal in response to c-MycV394D and therefore is not Miz-1-dependent. These data agree with other reports that c-MycV394D is not defective for all Myc-dependent repression (BarsyteLovejoy et al, 2004;Patel and McMahon, 2007). In addition, we find that c-MycV394D fully rescues the proliferation rate of myc-null cells (data not shown).…”

ARF antagonizes the ability of Miz-1 to inhibit p53-mediated transactivation

“…Similarly, Ziegelbauer et al (2004) reported that the loss of Miz-1 by RNA interference caused cells to accumulate in G1 and led to inhibition of cell proliferation in HepG2 cells. These data indicate that Miz-1 may also have some functions in promoting cell survival or proliferation other than the function in arresting cell growth (Sakurai et al, 2004;Patel and McMahon, 2007). Interestingly, we found that, different from Puma or Bax promoter, p53-target promoters p21 and Mdm2 showed little, if any, repression by Miz-1 (data not shown), and the mechanism behind this is still unclear at present.…”

The Bcl-2 apoptotic switch in cancer development and therapy

“…Furthermore, although Bim does not appear to be a direct transcriptional target of Myc, Bim levels were higher in premalignant B lymphoid cells from Em-myc than nontransgenic mice. Conversely, Myc overexpression lowers expression of Bcl-x L and Bcl-2 (Eischen et al, 2001;Egle et al, 2004b), perhaps by blocking the activity of the MIZ transcription factor, which seems to regulate bcl-2 expression (Patel and McMahon, 2006). We hypothesize that Bim is activated, and Bcl-x L /Bcl-2 suppressed, when Myc-driven proliferation exceeds a physiologic checkpoint, such as cytokine availability.…”