A point mutation in the RNA-binding domain I results in decrease of PKR activation in acute lymphoblastic leukemia

A point mutation in the RNA-binding domain I results in decrease of PKR activation in acute lymphoblastic leukemia

Autor Murad, J. M. Google Scholar
Tone, L. G. Google Scholar
Souza, L. R. de Google Scholar
De Lucca, F. L. Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo RNA-dependent protein kinase (PKR) mediates the antiviral activity of interferon and also has implications in cell growth, differentiation, and apoptosis. On the other hand, the tumor suppressor function of PKR is still controversial. PKR is a serine/threonine kinase that contains two RNA-binding domains (RBD-I and RBD-II) and RBD-I is critical for its activation. Site-directed mutagenesis studies indicated that a single amino acid substitution in RBD-I is sufficient to abolish the interaction of human PKR with RNA. Also, PKR mutants that are unable to bind RNA are inactive in vitro and have no antiproliferative activity in vivo. There have been no reports of mutations in the RNA-binding domains of PKR of tumor cells taken directly from patients.We investigated the presence of mutations in the RBD-I and RBD-II of PKR gene in children with acute lymphoblastic leukemia (ALL). the RNA extracted from bone marrow samples of 15 patients with ALL (5 patients T-lineage; 10 patients B-lineage) was used for to synthesize cDNA and amplify the sequences corresponding to RBD-I and RBD-II. the PCR products were subsequently cloned and sequenced. A point mutation was detected in the RBD-I of PKR from a patient with ALL of T-cell lineage that is located at cDNA in 50 A --> G (17 Tyr-->Cys). We also found that activation of a PKR mutant by the polyinosinic acid:polycytidylic acid (poly I:C) is impaired when compared with the wild-type PKR. Additional work is required to elucidate whether this point mutation plays a role in the formation and/or maintenance of leukemic cells. To our knowledge, this study is the first example of detection of a mutation in the RBD-I of PKR gene from tumor cells taken directly from patients. (C) 2004 Elsevier Inc. All rights reserved.
Palavra-chave protein kinase PKR
leukemia
point mutation
tumor suppressor gene
Idioma Inglês
Data de publicação 2005-01-01
Publicado em Blood Cells Molecules and Diseases. San Diego: Academic Press Inc Elsevier Science, v. 34, n. 1, p. 1-5, 2005.
ISSN 1079-9796 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 1-5
Fonte http://dx.doi.org/10.1016/j.bcmd.2004.08.025
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000226267100001
Endereço permanente http://repositorio.unifesp.br/handle/11600/28078

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