Role for PP2A in ARF signaling to p53

AUTOR(ES)

Moule, Madeleine G.

FONTE

National Academy of Sciences

RESUMO

Activation of the ARF–p53 tumor suppressor pathway is one of the cell's major defense mechanisms against cancer induced by oncogenes. The ARF–p53 pathway is dysfunctional in a high proportion of human cancers. The regulation of the ARF–p53 signaling pathway has not yet been well characterized. In this study polyoma virus (Py) is used as a tool to better define the ARF–p53 signaling pathway. Py middle T-antigen (PyMT) induces ARF, which consequently up-regulates p53. We show that Py small T-antigen (PyST) blocks ARF-mediated activation of p53. This inhibition requires the small T-antigen PP2A-interacting domain. Our results reveal a previously unrecognized role of PP2A in the modulation of the ARF–p53 tumor suppressor pathway.

Documentos Relacionados

• E1A signaling to p53 involves the p19ARF tumor suppressor
• Mdm2 Regulates p53 Independently of p19ARF in Homeostatic Tissues
• ARF Function Does Not Require p53 Stabilization or Mdm2 Relocalization
• A role for p53 in base excision repair
• P19ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2