The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex.
Nat Immunol
; 18(8): 911-920, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28628091
ABSTRACT
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression. Moreover, BTG2 in concert with PRMT1 efficiently blocked the proliferation of BCR-ABL1-transformed pre-B cells in vitro and in vivo. Our results identify a key molecular mechanism by which the BTG2-PRMT1 module regulates pre-B cell differentiation and inhibits pre-B cell leukemogenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína-Arginina N-Metiltransferasas
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Proteínas Inmediatas-Precoces
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Proteínas Supresoras de Tumor
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Linfopoyesis
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Proliferación Celular
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Quinasa 4 Dependiente de la Ciclina
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Células Precursoras de Linfocitos B
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Ciclina D3
Límite:
Animals
Idioma:
En
Año:
2017
Tipo del documento:
Article