title: Cooperation between ARID3A and p53 in the transcriptional activation of p21WAF1 in response to DNA damage.
abstract: ARID3A/DRIL1/Bright is a family member of the AT rich interaction domain (ARID) DNA-binding proteins that are involved in diverse biological processes. We have reported that p53 activates ARID3A transcription, and ARID3A overexpression induces G1 arrest. However, the role of ARID3A in the p53 pathway remains unclear. Here, we show that ARID3A cooperates with p53 to transcriptionally activate p21(WAF1), a p53-target gene important for cell-cycle arrest. ARID3A bound to its binding sites in the p21(WAF1) promoter in vivo and in vitro, and induced p21(WAF1) transcription in U2OS cells expressing wild-type p53 but not Saos-2 cells lacking p53. The co-expression of ARID3A with p53 cooperates to activate p21(WAF1) transcription and the stably transfected p21(WAF1) promoter. Mutation of the ARID3A binding sites reduced the p21(WAF1) promoter activity, and siRNA-based ARID3A knockdown suppressed the transcription of p21(WAF1), but not the proapoptotic NOXA and PUMA in response to DNA damage. Furthermore, p53 knockdown decreased ARID3A transcription, and, conversely, ARID3A overexpression and knockdown resulted in an increase or decrease in p53 stability, respectively. These results indicate both cooperative and interdependent roles for ARID3A and p53 in the transcriptional activation of p21(WAF1) in response to DNA damage.
authors.affiliation: Section of Molecular Craniofacial Embryology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Widya
authors.initials: W
authors.lastname: Lestari
authors.forename: Solachuddin J A
authors.initials: SJ
authors.lastname: Ichwan
authors.forename: Megumi
authors.initials: M
authors.lastname: Otsu
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yamada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Iseki
authors.forename: Shihoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Ikeda
mesh_terms: D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C490798:ARID3A protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53