EPSTEIN-BARR-VIRUS EXPLOITS THE NORMAL-CELL PATHWAY TO REGULATE RB ACTIVITY DURING THE IMMORTALIZATION OF PRIMARY B-CELLS

Citation
Ej. Cannell et al., EPSTEIN-BARR-VIRUS EXPLOITS THE NORMAL-CELL PATHWAY TO REGULATE RB ACTIVITY DURING THE IMMORTALIZATION OF PRIMARY B-CELLS, Oncogene, 13(7), 1996, pp. 1413-1421
Citations number
57
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,Biology,"Cell Biology
Journal title
ISSN journal
0950-9232
Volume
13
Issue
7
Year of publication
1996
Pages
1413 - 1421
Database
ISI
SICI code
0950-9232(1996)13:7<1413:EETNPT>2.0.ZU;2-U
Abstract
Infection of human primary B-lymphocytes with Epstein-Barr virus (EBV) drives quiescent cells into continual proliferation and results in th e outgrowth of immortal cell lines. This requires re-programming of th e mechanisms that, in the absence of appropriate antigenic stimulation , normally prevent the proliferation of B-lymphocyes. Since the Retino blastoma protein (pRb) and its relatives, p107 and p130, play critical roles in controlling the mammalian cell division cycle, we have inves tigated the expression and phosphorylation status of these proteins fo llowing EBV immortalisation of primary B-lymphocytes. In this report, me show that EBV drives the hyperphosphorylation of pRb. This is achie ved by a strategy involving the altered expression of several componen ts of the signal transduction pathway that normally regulates the phos phorylation status of pRb, including the up regulation of a number of cyclins and cyclin-dependent kinases and the down regulation of a subs et of cyclin-dependent kinase inhibitors. The net result is the format ion of active cyclin-dependent kinase complexes that are capable of ph osphorylating and inactivating pRb. The results presented here identif y the activation of a normal signal transduction pathway as an importa nt component of the strategy used by EBV to drive cell proliferation.