Authors: Irene López-Mateo, M. Ángeles Villaronga, Susana Llanos and Borja Belandia

Irene López-Mateo

Department of Cancer Biology; Instituto de Investigaciones Biomédicas Alberto Sols; CSIC-UAM; Madrid, Spain
These authors contributed equally to this work.

M. Ángeles Villaronga

Servicio de Otorrinolaringología; Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias; Oviedo, Spain
These authors contributed equally to this work.

Susana Llanos

Tumor Suppression Group; Spanish National Cancer Research Centre (CNIO); Madrid, Spain

Borja Belandia

Corresponding author: bbelandia@iib.uam.es
Department of Cancer Biology; Instituto de Investigaciones Biomédicas Alberto Sols; CSIC-UAM; Madrid, Spain

Abstract:
CREBZF is a member of the mammalian ATF/CREB family of transcription factors. Here, we describe a novel functional interaction between CREBZF and the tumor suppressor p53. CREBZF was identified in a yeast two-hybrid screen using HEY1, recently characterized as an indirect p53 activator, as bait. CREBZF interacts in vitro with both HEY1 and p53, and CREBZF expression stabilizes and activates p53. Moreover, CREBZF cooperates synergistically with HEY1 to enhance p53 transcriptional activity. On the other hand, partial depletion of endogenous CREBZF diminishes p53 protein levels and inhibits HEY1-mediated activation of p53. CREBZF-positive effects on p53 signaling may reflect, at least in part, an observed induction of posttranslational modifications in p53 known to prevent its degradation. CREBZF expression protects HCT116 cells from UV radiation-induced cell death. In addition, CREBZF expression confers sensitivity to 5-fluorouracil, a p53-activating chemotherapeutic drug. Our study suggests that CREBZF may participate in the modulation of p53 tumor suppressor function.

Received: July 16, 2012; Accepted: September 9, 2012; Published Online: September 14, 2012

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