LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis.

Acetylation Adaptor Proteins, Signal Transducing / metabolism Animals Cells, Cultured HEK293 Cells Hematopoiesis Humans LIM Domain Proteins / metabolism Leukopoiesis Mice Models, Molecular Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism Proto-Oncogene Proteins / metabolism Transcription Factors / metabolism Zebrafish Zebrafish Proteins / metabolism

Journal

Blood

ISSN: 1528-0020

Titre abrégé: Blood

Pays: United States

ID NLM: 7603509

Informations de publication

Date de publication:
03 10 2019

Historique:

received: 10 02 2019

accepted: 01 07 2019

pubmed: 2 8 2019

medline: 1 2 2020

entrez: 2 8 2019

Statut: ppublish

Résumé

Hematopoietic transcription factor LIM domain only 2 (LMO2), a member of the TAL1 transcriptional complex, plays an essential role during early hematopoiesis and is frequently activated in T-cell acute lymphoblastic leukemia (T-ALL) patients. Here, we demonstrate that LMO2 is activated by deacetylation on lysine 74 and 78 via the nicotinamide phosphoribosyltransferase (NAMPT)/sirtuin 2 (SIRT2) pathway. LMO2 deacetylation enables LMO2 to interact with LIM domain binding 1 and activate the TAL1 complex. NAMPT/SIRT2-mediated activation of LMO2 by deacetylation appears to be important for hematopoietic differentiation of induced pluripotent stem cells and blood formation in zebrafish embryos. In T-ALL, deacetylated LMO2 induces expression of TAL1 complex target genes

Identifiants

DOI: 10.1182/blood.2019000095 PMID: 31366618 PMC: PMC6888148

pubmed: 31366618

pii: S0006-4971(20)70774-3

doi: 10.1182/blood.2019000095

pmc: PMC6888148

doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0

LIM Domain Proteins 0

LMO2 protein, human 0

Proto-Oncogene Proteins 0

Transcription Factors 0

Zebrafish Proteins 0

lmo2 protein, zebrafish 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1159-1175

Informations de copyright

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