DeltaNp63 induces beta-catenin nuclear accumulation and signaling.
Publication/Presentation Date
5-1-2002
Abstract
The P53 homolog p63 encodes multiple proteins with transactivating, apoptosis-inducing, and oncogenic activities. We showed that p63 is amplified and that DeltaNp63 isotypes are overexpressed in squamous cell carcinoma (SCC) and enhance oncogenic growth in vitro and in vivo. Moreover, p53 associated with DeltaNp63alpha and mediated its degradation. Here, we report that DeltaNp63 associates with the B56alpha regulatory subunit of protein phosphatase 2A (PP2A) and glycogen synthase kinase 3beta (GSK3beta), leading to a dramatic inhibition of PP2A-mediated GSK3beta reactivation. The inhibitory effect of DeltaNp63 on GSK3beta mediates a decrease in phosphorylation levels of beta-catenin, which induces intranuclear accumulation of beta-catenin and activates beta-catenin-dependent transcription. Our results suggest that DeltaNp63 isotypes act as positive regulators of the beta-catenin signaling pathway, providing a basis for their oncogenic properties.
Volume
1
Issue
4
First Page
369
Last Page
379
ISSN
1535-6108
Published In/Presented At
Patturajan, M., Nomoto, S., Sommer, M., Fomenkov, A., Hibi, K., Zangen, R., Poliak, N., Califano, J., Trink, B., Ratovitski, E., & Sidransky, D. (2002). DeltaNp63 induces beta-catenin nuclear accumulation and signaling. Cancer cell, 1(4), 369–379. https://doi.org/10.1016/s1535-6108(02)00057-0
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
12086851
Department(s)
Department of Pediatrics
Document Type
Article