Mechanisms of Cr(VI)-induced p53 activation: the role of phosphorylation, mdm2 and ERK

Authors
Citation
Sw. Wang et Xl. Shi, Mechanisms of Cr(VI)-induced p53 activation: the role of phosphorylation, mdm2 and ERK, CARCINOGENE, 22(5), 2001, pp. 757-762
Citations number
54
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
22
Issue
5
Year of publication
2001
Pages
757 - 762
Database
ISI
SICI code
0143-3334(200105)22:5<757:MOCPAT>2.0.ZU;2-H
Abstract
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.