Altmetric

Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia

Title: Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia
Authors: Bond, J
Domaschenz, R
Roman-Trufero, M
Sabbattini, P
Ferreiros-Vidal, I
Gerrard, G
Asnafi, V
Macintyre, E
Merkenschlager, M
Dillon, N
Item Type: Journal Article
Abstract: Ikaros and Foxp1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies. We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL). We also identify the Gpr132 gene, which encodes the orphan G protein-coupled receptor G2A, as a novel target for Foxp1. Increased expression of Foxp1 enhanced Gpr132 transcription and caused cell cycle changes, including G2 arrest. Co-expression of wild-type Ikaros, but not IK6, displaced Foxp1 binding from the Gpr132 gene, reversed the increase in Gpr132 expression and inhibited G2 arrest. Analysis of primary ALL samples revealed a significant increase in GPR132 expression in IKZF1-deleted BCR-ABL negative patients, suggesting that levels of wild-type Ikaros may influence the regulation of G2A in B-ALL. Our results reveal a novel effect of Ikaros haploinsufficiency on Foxp1 functioning, and identify G2A as a potential modulator of the cell cycle in Ikaros-deleted B-ALL.
Issue Date: 30-Aug-2016
Date of Acceptance: 13-Aug-2016
URI: http://hdl.handle.net/10044/1/40030
DOI: https://dx.doi.org/10.18632/oncotarget.11688
ISSN: 1949-2553
Publisher: Impact Journals
Start Page: 65923
End Page: 65936
Journal / Book Title: Oncotarget
Volume: 7
Issue: 40
Copyright Statement: Copyright @ 2016 Impact Journals, LLC. This paper is licenced under a CC-BY 3.0 (https://creativecommons.org/licenses/by/3.0/)
Keywords: B cell cycle
Foxp1
GPR132
Ikaros
acute leukemia
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx