Research Perspective Volume 2, Issue 12 pp 1023—1029

Figure 1. Zfra in the mitochondrial pathway of apoptosis. UV light induces Zfra phosphorylation (pZfra) at Ser8 and translocation to the nuclei (Route 1). Zfra rapidly undergoes de-phosphorylation and degradation in the nuclei [29]. However, in response to stimuli for the mitochondrial pathway of apoptosis, Zfra becomes Ser8-phosphorylated and relocates, along with p53 and WOX1, to the mitochondria. Ectopic Zfra significantly downregulates Bcl-2 and Bcl-xL (Route 2), blocks cytochrome c release by interacting with voltage-dependent anion channel (VDAC) (Route 3), and yet induces dissipation of mitochondrial membrane potential [29]. Alternatively, Zfra probably interacts with cytochrome c to block its release from the mitochondria. Zfra binds and blocks the apoptotic function of WOX1 (Route 4). Overexpressed WOX1 induces cytochrome c release (Route 5) [29]. By the same token, Zfra blocks apoptotic function of p53 in the mitochondria.