Appropriate subcellular localization of proteins is crucial for regulating their
functions. Both p53 and the BH3-only Bid play roles in the development and the
treatment of hepatocellular carcinoma. Bid genomic loci contain p53-binding DNA
response elements and Bid can mediate p53-dependent transactivation. However, how
these molecules function in the liver cells is not completely known. In this study, liver
cells were stimulated by etoposide to damage DNA, and the location and the interaction
of Bid and p53 were examined by Western blot, immonocchemical staining,
immunoprecipitation and siRNA methods. Our data showed that etoposide-induced
DNA damage significantly induced p53 and Bid nuclear export. When cells were
stimulated by etoposide, p53 could, through the interaction with Bid, cause
translocation of Bid from the nucleus to the cytoplasm and on to its ultimate location in
the mitochondria. Moreover, p53 physically associated with Bid, and both p53 and Bid
cooperatively promoted cell death induced by etoposide. Knockdown of Bid expression
notably attenuated cell death induced by etoposide and also released p53 from the
mitochondria. In conclusion, these findings reveal a novel mechanism how p53
facilitates Bid nuclear export and how both of them interact in the nucleus and the
mitochondria to induce apoptosis in response to etoposide-induced DNA damage.
Keywords: Bid, cell death, etoposide, hepatocellular carcinoma, mitochondria,
nucleus, p53.