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. Author manuscript; available in PMC: 2014 May 1.
Published in final edited form as: Stem Cell Res. 2013 Feb 5;10(3):428–441. doi: 10.1016/j.scr.2013.01.010

Figure 6. Model of ETO-induced PCD (Charontosis) in mESCs.

Figure 6

Etoposide promotes p53 translocation from the cytoplasm to the nucleus to promote transcription of target genes involved in cell death. This activity is reduced following treatment with pifithrin α (PFα). A portion of p53 remains outside the nucleus and presumably translocates to mitochondria to inactivate pro-survival Bcl-2 family members. Pifithrin μ (PFμ) can reduce p53 association with mitochondria, resulting in protection from death. The mitochondria may release ROS, which can disrupt the lysosomal membrane and cause release of cathepsins, which cleave specific target proteins. P53 may also translocate to the lysosome and result in the release of cathepsins. The activities of several cathepsins are inhibited by zFA and zFF, which reduce ETO-induced PCD. Bafilomycin A1 (BA1) inhibits lysosomal acidification, resulting in decreased cathepsin activity and reduced PCD. Spautin1 can inhibit ubiquitin-specific proteases that can regulate p53, although other targets are known to exist. Finally, EndoG is released from mitochondria to induce DNA fragmentation.