The present study investigated the molecular mechanisms of p53 activation i
nduced by Cr(VI), using human lung epithelial A549 cells. Cr(VI) increased
both protein level and transactivation ability of p53 protein. The activati
on of p53 is at the protein level instead of the transcriptional level. The
degradation of p53 was dramatically decreased upon stimulation by Cr(VI).
In addition, Cr(VI) treatment decreased the interaction of p53 with mdm2 pr
oto-oncoprotein, which blocks the transactivation ability of p53 and promot
es the degradation of p53 protein. In response to Cr(VI) treatment, p53 pro
tein became phosphorylated and acetylated at Ser15 and Lys382, respectively
. The phosphorylation levels at either Ser20 or Ser392 did not show any sig
nificant alterations. Since previous studies report that it is Ser20 and no
t Ser15 phosphorylation that contributes to mdm2 dissociation from p53, the
results obtained from the current investigation suggest a different mechan
ism: Ser15 instead of Ser20 may play a key role in the dissociation of mdm2
in response to Cr(VI). Erk, a member of mitogen-activated protein kinase,
acts as the upstream kinase for the phosphorylation of the p53 Ser15 site.