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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimetabolites, Antineoplastic / pharmacology
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Basic-Leucine Zipper Transcription Factors / genetics*
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Basic-Leucine Zipper Transcription Factors / metabolism
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COS Cells
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Cell Death / drug effects
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Cell Death / radiation effects
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Cell Line, Tumor
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Chlorocebus aethiops
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Fluorouracil / pharmacology
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Gene Expression Regulation* / drug effects
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Gene Expression Regulation* / radiation effects
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Genes, Reporter
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Humans
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Luciferases
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Plasmids
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Protein Binding
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Signal Transduction / drug effects
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Signal Transduction / radiation effects
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Transcription, Genetic* / drug effects
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Transcription, Genetic* / radiation effects
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism
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Two-Hybrid System Techniques
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Ultraviolet Rays
Substances
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Antimetabolites, Antineoplastic
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Basic Helix-Loop-Helix Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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CREBZF protein, human
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Hairy, HRT1 protein
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Recombinant Fusion Proteins
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Repressor Proteins
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Tumor Suppressor Protein p53
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Luciferases
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Fluorouracil