SP1 and RARα regulate AGAP2 expression in cancer

Doush, Y., Surani, A.A. ORCID: 0000-0002-5180-9075, Navarro-Corcuera, A., McArdle, S. ORCID: 0000-0001-6929-9782, Billett, E.E. ORCID: 0000-0001-8245-6519 and Montiel-Duarte, C. ORCID: 0000-0002-9144-8809, 2019. SP1 and RARα regulate AGAP2 expression in cancer. Scientific Reports, 9: 390. ISSN 2045-2322

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AGAP2 (Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2) isoform 2 is considered a proto-oncogene, but not much is known about AGAP2 gene expression regulation. To get some insight into this process, AGAP2 proximal promoter was cloned and characterised using reporter assays. We have identified SP1 as a transcription factor bound to AGAP2 promoter and required for AGAP2 expression in two different types of cancer cells (KU812, a chronic myeloid leukaemia cell line; and DU145, a prostate cancer cell line): silencing SP1 decreased AGAP2 protein levels. We have also found that all-trans retinoic acid (ATRA) treatment increased AGAP2 protein levels in both cell lines whilst curcumin treatment reduced ATRA-mediated AGAP2 increase. Furthermore, chromatin immunoprecipitation studies revealed the presence of RARα, RXRα and the lysine acetyl transferase PCAF in AGAP2 promoter. Our results provide a novel understanding of AGAP2 expression regulation that could be beneficial to those patients with cancers where AGAP2 is overexpressed.

Item Type: Journal article
Publication Title: Scientific Reports
Creators: Doush, Y., Surani, A.A., Navarro-Corcuera, A., McArdle, S., Billett, E.E. and Montiel-Duarte, C.
Publisher: Nature Publishing Group
Date: 23 January 2019
Volume: 9
ISSN: 2045-2322
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 17 Jan 2019 14:15
Last Modified: 04 Jul 2022 15:30
URI: https://irep.ntu.ac.uk/id/eprint/35604

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