Specific changes in the posttranslational regulation of nucleolin in lymphocytes from patients infected with human immunodeficiency virus.
Lymphocytes isolated from human immunodeficiency virus (HIV)-infected patients have dysregulated cell-cycle 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.
Galati
Domenico
D
Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi," Seconda Universita' degli Studi di Napoli, Napoli, Italy.
Paiardini
Mirko
M
Cervasi
Barbara
B
Albrecht
Helmut
H
Bocchino
Marialuisa
M
Costantini
Andrea
A
Montroni
Maria
M
Magnani
Mauro
M
Piedimonte
Giuseppe
G
Silvestri
Guido
G
D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000276:immunology / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D019926:Cyclin B / Q000276:immunology / Q000502:physiology; D056744:Cyclin B1; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D013912:Threonine / Q000378:metabolism; D000097796:Nucleolin
D016203:CDC2 Protein Kinase; D003208:Concanavalin A; D019926:Cyclin B; D056744:Cyclin B1; D007376:Interleukin-2; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D013912:Threonine; D000097796:Nucleolin; C534699:CCNB1 protein, human