Proteomics

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NPM and NPM-MLF1 interact with chromatin remodeling complexes and influence their recruitment to specific genes


ABSTRACT: Nucleophosmin (NPM1) is either frequently mutated or subjected to chromosomal translocation in acute myeloid leukemia (AML). NPM protein is primarily located in the nucleus, but the recurrent NPMc+ mutation is characterized by cytoplasmic localization and leukemogenic properties. Similarly, the NPM-MLF1 translocation product favors the partial cytoplasmic retention of NPM. Regardless of their common cellular distribution, NPM-MLF1 malignancies engender different effects on hematopoiesis compared to NPMc+ counterparts, highlighting possible aberrant nuclear function(s) of NPM in NPMc+ and NPM-MLF1 AML. We performed a proteomics analysis and found that NPM and NPM-MLF1 interact with chromatin remodeling complexes of the ISWI family, as well as with NuRD and P/BAF complexes. Accordingly, NPM and NPM-MLF1 are recruited to transcriptionally active or repressed genes along with NuRD and P/BAF elements. Although the overall gene expression program in NPM knockdown cells is similar to that resulting from NPMc+ and is consistent with loss of nuclear function of NPM, NPM-MLF1 expression differentially altered gene transcription regulated by NPM. The abnormal gene regulation imposed by NPM-MLF1 is characterized by enhanced recruitment of NuRD to gene regulatory regions. Thus, different mechanisms orchestrate the deregulation of NPM function in NPMc+ -versus NPM1-MLF1- associated leukemia.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Erythrocyte, Cell Suspension Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Eric Milot  

LAB HEAD: Dr Milot Eric

PROVIDER: PXD012305 | Pride | 2019-10-18

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
18023-MOCK1.raw Raw
18024-MOCK2.raw Raw
18025-NPM1.raw Raw
18026-NPM2.raw Raw
18027-NPM3.raw Raw
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Publications

NPM and NPM-MLF1 interact with chromatin remodeling complexes and influence their recruitment to specific genes.

Darracq Anaïs A   Pak Helen H   Bourgoin Vincent V   Zmiri Farah F   Dellaire Graham G   Affar El Bachir EB   Milot Eric E  

PLoS genetics 20191101 11


Nucleophosmin (NPM1) is frequently mutated or subjected to chromosomal translocation in acute myeloid leukemia (AML). NPM protein is primarily located in the nucleus, but the recurrent NPMc+ mutation, which creates a nuclear export signal, is characterized by cytoplasmic localization and leukemogenic properties. Similarly, the NPM-MLF1 translocation product favors the partial cytoplasmic retention of NPM. Regardless of their common cellular distribution, NPM-MLF1 malignancies engender different  ...[more]

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