EIF-5A Regulates P53 And P53-dependent Apoptosis

eIF5A was originally designated as an "eukaryotic translation initiation factor" and it is the only cellular protein known to contain the unique animo acid hypusine, a modification that appears to be required for cell proliferation. Recent data have shown it to be also involved in apoptosis. However, the actual function of eIF5A in apoptosis is still unknown. Our findings, for the first time, revealed a new biological activity for eIF5A as the regulator of p53. Overexpression of eIF5A or its EFP domain resulted in up-regulation of p53, and silencing eIF5A by siRNA reduced p53 protein level. Further analysis by RT-PCR showed eIF5A activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well-known target genes of p53. In contrast, a point mutant of eIF5A, hypusination being abolished, was revealed to be functionally defective in p53 up-regulation. Overexpression of eIF5A led to a p53-dependent apoptosis, or sensitized cells to induction of apoptosis by chemotherapeutic agents. However, when eIF5A interacted with its novel partner, syntenin, the eIF5A-induced increase in p53 protein level was significantly inhibited. Therefore, eIF5A seems to be a previously un-recognized regulator of p53 that may define a new pathway for p53-dependent apoptosis, and syntenin might regulate p53 by balancing the regulation of eIF5A signaling to p53 for apoptosis.