FMNL1 : caracterização de um novo gene humano relacionado com a familia das forminas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

Formins are proteins that are involved in processes such as morphogenesis, embryonic differentiation, cytokinesis, cell polarity and survival. The formins are multidomain proteins that are conserved from plants to fungi and vertebrates. A search of the ORESTES database, generated from the Human Cancer Genome Project, identified 2 ESTs that were similar to the Formin-related proteins. The aim of this study was to obtain the full-Iength sequence ofthis new gene, the primary structure ofthe protein coded by this gene, its subcellular localization and to characterize its possible interaction with other proteins in addition to functional studies. In an attempt to obtain the full-Iength sequence of this rnRNA, searches in the human genome database at NCBI (National Center for Biotechnology Information) and molecular biology techniques were performed. The whole coding sequence ofthis gene was named Human Leukocyte Formin and was deposited at the human genome database at NCBI (GenBank Accession No. AY278319). Later, based on the HUGO Gene Nomenc1ature Committee, the new gene was renamed formin-like 1 and the symbol FMNLl will herein be used. The production of a polyc1onal antibody specific for the protein FMNLl allowed the study of the protein s expression in different human tissues. Using the Westem Blotting technique, a preferential expression of this protein in lymphoid malignancies was observed. Among normal tissues, a low expression in lymph node, peripheral blood mononuClear cells and in CD19- cells (when compared with CD19+ cells from normal tonsils) was observed. Among the malignant celllines, a high expression of the protein was detected in MOLT-4 and the Jurkat cell line, when compared with myeloid cancer cell lines, suggesting a preferential expression of FMNLl in lymphoid malignancies. Moreover, a high expression of the protein in peripheral blood mononuc1ear cells from 20 chronic lymphocytic leukemia patients was observed when compared with peripheral blood mononuc1ear cells of normal donors. When the expression of FMNLl protein was compared among different histological types of non-Hodgkin s lymphoma (NHL) and reactive lymph nodes, again, a preferential expression of the protein in the malignant tissue was detected and the T cell NHL presented the highest expression. This new protein is located in the cytoplasm of the cells, as observed by confocal microscopy and confirmed by separation of the cellular ftaction. With regard to the interactions ofthis new protein, an association ofFMNLI with AKT was detected, and this association was not dependent on AKT activation. A decrease in FMNLI expression in 2 cancer celllines after caspase activation was also detected. ln conclusion, the preferential expression of FMNLI in lymphoid malignancies and its association with AKT, suggests the role ofFMNLI in cell survival and a possible role in the pathophysiology ofhematological malignancies

ASSUNTO(S)

proteina quinase b neoplasias hematologicas

ACESSO AO ARTIGO

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