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Specific Changes in the Posttranslational Regulation of Nucleolin in Lymphocytes from Patients Infected with Human Immunodeficiency Virus [with Discussion]

Domenico Galati, Mirko Paiardini, Barbara Cervasi, Helmut Albrecht, Marialuisa Bocchino, Andrea Costantini, Maria Montroni, Mauro Magnani, Giuseppe Piedimonte and Guido Silvestri
The Journal of Infectious Diseases
Vol. 188, No. 10 (Nov. 15, 2003), pp. 1483-1491
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30075753
Page Count: 9
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Specific Changes in the Posttranslational Regulation of Nucleolin in Lymphocytes from Patients Infected with Human Immunodeficiency Virus [with Discussion]
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Abstract

Lymphocytes isolated from human immunodeficiency virus (HIV)-infected patients have dysregulated cellcycle control, consisting of increased activation of the cyclin B1/p34 cdc2 complex and abnormal nucleolar structure. To better characterize the molecular features of the HIV-associated cell-cycle perturbations, we performed a detailed analysis of the posttranslational regulation of nucleolin, a key structural protein in the nucleolus. We found that, in concanavalin A-stimulated lymphocytes from HIV-infected patients, the inappropriate activation of the cyclin B1/p34 cdc2 kinase complex is temporally associated with increased threonine phosphorylation, augmented fragmentation, and prominent extranuclear and cell-surface localization of nucleolin. Importantly, increased lymphocyte apoptosis is observed at the time of cell-surface localization of nucleolin. These results may delineate a direct molecular link between abnormal activation of cyclin B1/p34 cdc2 and the changes in the nucleolar structure, thus providing a better molecular definition of HIV-associated cell-cycle dysregulation.

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