Counteracting MDM2-induced HIPK2 downregulation restores HIPK2/p53 apoptotic signaling in cancer cells.
FEBS Lett
; 584(19): 4253-8, 2010 Oct 08.
Article
em En
| MEDLINE
| ID: mdl-20849851
ABSTRACT
Homeodomain-interacting protein kinase-2 (HIPK2) is a crucial regulator of p53 apoptotic function by phosphorylating serine 46 (Ser46) in response to DNA damage. In tumors with wild-type p53, its tumor suppressor function is often impaired by MDM2 overexpression that targets p53 for proteasomal degradation. Likewise, MDM2 targets HIPK2 for protein degradation impairing p53-apoptotic function. Here we report that zinc antagonised MDM2-induced HIPK2 degradation as well as p53 ubiquitination. The zinc inhibitory effect on MDM2 activity leads to HIPK2-induced p53Ser46 phosphorylation and p53 pro-apoptotic transcriptional activity. These results suggest that zinc derivatives are potential molecules to target the MDM2-induced HIPK2/p53 inhibition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Proteína Supressora de Tumor p53
/
Proteínas Serina-Treonina Quinases
/
Apoptose
/
Proteínas Proto-Oncogênicas c-mdm2
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Itália