Imperial College London
Alternate

ProfessorMatthiasMerkenschlager

Faculty of Medicine, Institute of Clinical Sciences

Professor of Cell Biology
 
 
 
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Contact

 

+44 (0)20 3313 8239matthias.merkenschlager

 
 
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Location

 

5.11DLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bond:2016:10.18632/oncotarget.11688,
author = {Bond, J and Domaschenz, R and Roman-Trufero, M and Sabbattini, P and Ferreiros-Vidal, I and Gerrard, G and Asnafi, V and Macintyre, E and Merkenschlager, M and Dillon, N},
doi = {10.18632/oncotarget.11688},
journal = {Oncotarget},
pages = {65923--65936},
title = {Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia},
url = {http://dx.doi.org/10.18632/oncotarget.11688},
volume = {7},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Bond,J
AU  - Domaschenz,R
AU  - Roman-Trufero,M
AU  - Sabbattini,P
AU  - Ferreiros-Vidal,I
AU  - Gerrard,G
AU  - Asnafi,V
AU  - Macintyre,E
AU  - Merkenschlager,M
AU  - Dillon,N
DO  - 10.18632/oncotarget.11688
EP  - 65936
PY  - 2016///
SN  - 1949-2553
SP  - 65923
TI  - Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia
T2  - Oncotarget
UR  - http://dx.doi.org/10.18632/oncotarget.11688
UR  - http://hdl.handle.net/10044/1/40030
VL  - 7
ER  -
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