Rabbit Anti-Human GNL3 monoclonal antibody, clone 4I30M3

Nucleostemin was first identified in neural stem cells and has become a focus of research in cell cycle control. tumorigenesis and cellular senescence As the biology of nucleostemin begins to be unveiled in multiple species, an ensuing task is to resolve the apparent differences between the functions of mammahan and invertebrate nucleostemin and its homologues, an issue of pressing interest given the role of nucleostemin in stem cell self-renewal and tissue regeneration A genome-wide search reveals that nucleostemin and its closest homologue, GNL3L only emerge as separate genes in vertebrates and possess conserved protein sequences as evolution proceeded to the Mammalia. The invertebrate orthologue of nucleostemin and GNL3L resembles GNL3L more than it does nucleostemin in function, raising the idea that nucleostemin acquires new properties while GNL3L inherits an evolutionarily fixed role, and that the birth of nucleostemin may signify the appearance of new functional features in the vertebrate lineage. (C) 2009 Elsevier Ltd. All rights reserved

Nucleostemin (NS)/GNL3 protein has been recently documented to be a nucleolar protein that was abundantly expressed in stem cells and cancer cells. Herein, we showed that NS was upregulated in HCC tissues and the expression of NS was inversely correlated with that of p53. Overexpression of NS predicted significantly worsened prognosis in HCC patients, suggesting that NS might serve as a prognostic marker of HCC. In addition, we found that depletion of NS sensitized HCC cells to sorafenib-induced apoptosis. Moreover, we found that the mechanism underlying NS-mediated sorafenib resistance involved dysregulated expression of p53, and downstream Bax and Bcl-2 proteins. NS interacted with p53 in HCC cells. Depletion of NS increased the expression of p53 and Bax, whereas impaired the level of cellular Bcl-2. Interference of NS enhanced the cytotoxic effects of sorafenib in HCC cells. Furthermore, ectopic expression of NS impaired the apoptosis of HCC cells following sorafenib exposure. Therefore, NS may contribute to sorafenib resistance in HCC cells through the modulation of p53 pathway and Bcl-2 proteins. These findings indicated that the combination of silencing NS expression and sorafenib treatment is a promising therapeutic strategy in treatment of HCC. (C) 2016 Elsevier GmbH. All rights reserved.