c-Myb, the cellular homologue of the transforming gene of the avian myeloblastosis virus, is preferentially expressed in all hematopoietic lineages, including T and B lymphocyte lineages, In T lymphocytes, c-Myb expression appears to be required for cell cycle progression and proliferation, To further investigate the role of c-Myb in T cell proliferation and survival, interleukin (IL) 2-dependent CTLL-2 cells were transfected with a constitutively active c-myb or with a c-myb antisense construct able to down-regulate endogenous Myb levels, and the transfectants were assessed for proliferation and survival in low concentrations of IL-2 and for susceptibility to dexamethasone-induced apoptosis, Compared with control cells, CTLL-2 cells constitutively expressing c-Myb proliferate in low concentrations of IL-2 and are less susceptible to apoptosis induced bq IL-2 deprivation or treatment with dexamethasone. In contrast, cells transfected with an antisense c-myb construct do not proliferate in Low concentrations of IL-2 and undergo apoptosis upon IL-2 deprivation or dexamethasone treatment more rapidly than parental cells, Overexpression of c-Myb was accompanied by up-regulation of BCL-2 expression, In transient transfection assays, the murine bcl-2 promoter was efficiently transactivated by c-Myb, but such effect was observed also in cells transfected with a DNA binding-deficient c-myb construct, Moreover, in gel retardation assays, a 38-bp oligomer in the shortest bcl-2 promoter segment regulated by c-Myb formed a specific complex with nuclear extracts from c-Myb transfected CTLL-2 cells, Thus, these results strongly suggest that c-Myb? in addition to regulating T cell proliferation, protects T lymphocytes from apoptosis by induction of BCL-2 expression, which involves a c-Myb-dependent mechanism of promoter regulation.
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|Anno di pubblicazione:||1997|
|Titolo:||Resistance to apoptosis in CTLL-2 cells constitutively expressing c-Myb is associated with induction of bcl-2 expression and Myb-dependent regulation of bcl-2 promoter activity|
|Autori:||P. Salomoni; D. Perrotti; R. Martinez; C. Franceschi; B. Calabretta|
|Autori interni:||SALOMONI, Paolo |
|Rivista:||PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA|
|Appare nelle tipologie:||Articolo su rivista|
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