title: DEC1 coordinates with HDAC8 to differentially regulate TAp73 and ΔNp73 expression.
abstract: P73, a member of the p53 family, plays a critical role in neural development and tumorigenesis. Due to the usage of two different promoters, p73 is expressed as two major isoforms, TAp73 and ΔNp73, often with opposing functions. Here, we reported that transcriptional factor DEC1, a target of the p53 family, exerts a distinct control of TAp73 and ΔNp73 expression. In particular, we showed that DEC1 was able to increase TAp73 expression via transcriptional activation of the TAp73 promoter. By contrast, Np73 transcription was inhibited by DEC1 via transcriptional repression of the ΔNp73 promoter. To further explore the underlying mechanism, we showed that DEC1 was unable to increase TAp73 expression in the absence of HDAC8, suggesting that HDAC8 is required for DEC1 to enhance TAp73 expression. Furthermore, we found that DEC1 was able to interact with HDAC8 and recruit HDAC8 to the TAp73, but not the ΔNp73, promoter. Together, our data provide evidence that DEC1 and HDAC8 in differentially regulate TAp73 and ΔNp73 expression, suggesting that this regulation may lay a foundation for a therapeutic strategy to enhance the chemosensitivity of tumor cells.
authors.affiliation: Comparative Oncology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Comparative Oncology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Comparative Oncology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Yong-Sam
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Comparative Oncology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C107989:BHLHE40 protein, human; C000606460:TP73 protein, human; C000606369:delta Np73 protein, human; C409470:HDAC8 protein, human