RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.

The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leuke...

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Main Authors: Wilkinson, A, Ballabio, E, Geng, H, North, P, Tapia, M, Kerry, J, Biswas, D, Roeder, R, Allis, C, Melnick, A, de Bruijn, M, Milne, T
Format: Journal article
Language:English
Published: 2013
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author Wilkinson, A
Ballabio, E
Geng, H
North, P
Tapia, M
Kerry, J
Biswas, D
Roeder, R
Allis, C
Melnick, A
de Bruijn, M
Milne, T
author_facet Wilkinson, A
Ballabio, E
Geng, H
North, P
Tapia, M
Kerry, J
Biswas, D
Roeder, R
Allis, C
Melnick, A
de Bruijn, M
Milne, T
author_sort Wilkinson, A
collection OXFORD
description The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product.
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spelling oxford-uuid:ad651e9c-c9f0-4780-abf9-00a909ff8b162022-03-27T03:35:20ZRUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ad651e9c-c9f0-4780-abf9-00a909ff8b16EnglishSymplectic Elements at Oxford2013Wilkinson, ABallabio, EGeng, HNorth, PTapia, MKerry, JBiswas, DRoeder, RAllis, CMelnick, Ade Bruijn, MMilne, TThe Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product.
spellingShingle Wilkinson, A
Ballabio, E
Geng, H
North, P
Tapia, M
Kerry, J
Biswas, D
Roeder, R
Allis, C
Melnick, A
de Bruijn, M
Milne, T
RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
title RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
title_full RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
title_fullStr RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
title_full_unstemmed RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
title_short RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
title_sort runx1 is a key target in t 4 11 leukemias that contributes to gene activation through an af4 mll complex interaction
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