The European flounder (Platichthys flesus) TP53 functions as a temperature-sensitive transcription factor which inhibits cell growth in yeast.
Numerous studies focus on biological roles of the TP53 tumor suppressor gene in mammals but little is known about the actual function of TP53 in lower vertebrates. In this study, we used an in vivo functional assay in yeast to address the transactivation capacity of the flounder TP53 protein. We showed that the flounder TP53 acts as a sequence-specific transcription factor which is able to transactivate various human promoters containing a p53-responsive element (RE). This transcriptional activity was completely abrogated in the Val147Glu TP53 mutant previously identified in two flounder hepatic hyperplasia. In addition, we showed that the wild-type (wt) flounder TP53 but not the Val147Glu mutant inhibits cell growth when expressed in yeast. We finally reported that transcription regulation and growth inhibition by the wild-type flounder TP53 is temperature-dependent. The flounder TP53 optimal temperature appeared lower than those reported for the Xenopus and human homologues.
Cachot
J
J
Laboratory of Ecotoxicology, University of Le Havre, 25 rue P. Lebon, Le Havre Cedex, France. Jerome.Cachot@univ.lehavre.fr
Flaman
J M
JM
Frébourg
T
T
Leboulenger
F
F
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D005432:Flounder / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020125:Mutation, Missense; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53