Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin.
Blood
; 131(12): 1325-1336, 2018 03 22.
Article
em En
| MEDLINE
| ID: mdl-29437589
ABSTRACT
B-cell lymphomas are heterogeneous blood disorders with limited therapeutic options, largely because of their propensity to relapse and become refractory to treatments. Carabin, a key suppressor of B-cell receptor signaling and proliferation, is inactivated in B-cell lymphoma by unknown mechanisms. Here, we identify prolyl 4-hydroxylase 2 (P4HA2) as a specific proline hydroxylase of Carabin. Carabin hydroxylation leads to its proteasomal degradation, thereby activating the Ras/extracellular signal-regulated kinase pathway and increasing B-cell lymphoma proliferation. P4HA2 is undetectable in normal B cells but upregulated in the diffuse large B-cell lymphoma (DLBCL), driving Carabin inactivation and lymphoma proliferation. Our results indicate that P4HA2 is a potential prognosis marker for DLBCL and a promising pharmacological target for developing treatment of molecularly stratified B-cell lymphomas.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Linfoma Difuso de Grandes Células B
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Sistema de Sinalização das MAP Quinases
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Proteínas Adaptadoras de Transdução de Sinal
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Proliferação de Células
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Prolil Hidroxilases
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article