Caspase-3-resistant uncleavable form of acidic leucine-rich nuclear phosphoprotein 32B potentiates leukemic cell apoptosis.
Mol Med Rep
; 11(4): 2813-8, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25483709
ABSTRACT
One member of the highly conserved acidic leucinerich nuclear phosphoprotein 32 kDa (ANP32) family of proteins, ANP32B, is critical for normal development, as demonstrated by a study in ANP32Bdeficient mice. Another study indicated that ANP32B was a direct substrate of caspase3, and was primarily cleaved at the sequence AlaGluValAsp, following Asp163. To investigate the significance of ANP32B cleavage in apoptosis, leukemic U937T cell lines were generated with inducible expression of ANP32B(wild type; WT), the uncleavable mutant ANP32B(D163A) and the Nterminal fragment ANP32B(1163). Notably, overexpression of ANP32B(WT) and ANP32B(D163A) moderately increased and significantly enhanced etoposideinduced apoptosis and caspase3 activation, whereas expression of ANP32B(1163) produced no effect. Two hypotheses have been generated, which may explain the distinct roles of the various ANP32B forms i) ANP32B(WT) and ANP32B(D163A) localize in the nucleus while ANP32B(1163) mainly resides in the cytosol; or ii) ANP32B(WT) and ANP32B(D163A), but not ANP32B(1163), inhibit the expression of the antiapoptotic protein Bcl2. Based on these observations, caspase3resistant uncleavable ANP32B(D163A) is hypothesized to be proapoptotic in leukemic cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Leucemia
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Apoptosis
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Caspasa 3
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Dominios y Motivos de Interacción de Proteínas
Límite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2015
Tipo del documento:
Article