Critical role of ARID3B in the expression of pro-apoptotic p53-target genes and apoptosis

ARID3A and ARID3B are transcriptional targets of p53. Recently, it has been reported that ARID3A plays a critical role in the transcriptional activation of pro-arrest p21 in response to DNA damage. However, the role of ARID3B in the p53 regulatory pathway remains poorly understood. Here we show that...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2015-12, Vol.468 (1-2), p.248-254
Main Authors: Pratama, Endrawan, Tian, Xiaohui, Lestari, Widya, Iseki, Sachiko, Ichwan, Solachuddin J.A., Ikeda, Masa-Aki
Format: Article
Language:English
Subjects:
Apoptosis
ARID3A
ARID3B
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 - genetics
DNA Damage
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene expression
Gene Expression Regulation
Gene Silencing
Humans
p53
Promoter Regions, Genetic
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptional Activation
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary:ARID3A and ARID3B are transcriptional targets of p53. Recently, it has been reported that ARID3A plays a critical role in the transcriptional activation of pro-arrest p21 in response to DNA damage. However, the role of ARID3B in the p53 regulatory pathway remains poorly understood. Here we show that ARID3A and ARID3B specifically bind to putative ARID3-binding sites in p53 target genes in vitro and in vivo. ARID3B and, to a lesser extent, ARID3A silencing blocked transcriptional activation of pro-apoptotic p53 target genes, such as PUMA, PIG3, and p53. Furthermore, ectopic ARID3B, to a lesser extent, ARID3A expression activated the pro-apoptotic gene expression, and only ARID3B induced apoptosis. Finally, ARID3B but not ARID3A silencing blocked apoptosis induction following DNA damage. These results indicated that, although ARID3B and ARID3A share overlapping functions, ARID3B play a key role in the expression of pro-apoptotic p53-target genes and apoptosis. •ARID3A and ARID3B bind to ARID3-binding sites in the p53 target genes.•ARID3B silencing blocked expression of pro-apoptotic p53-target genes.•ARID3B overexpression activated transcription of pro-apoptotic p53-target genes.•Ectopic ARID3B but not ARID3A expression induced apoptosis.•ARID3B but not ARID3A silencing blocked apoptosis following DNA damage.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2015.10.121