Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel-/- B cells.

摘要: Aberrant overexpression of the c-rel protooncogene is associated with lymphoid malignancy, while deletion produces severe lymphoproliferative defects and immunodeficiency. To investigate mechanism c-rel-induced proliferation cell cycle progression in B lymphocytes, we have compared signaling events elicited through BCR c-rel−/− wild-type cells. stimulation cells fails to induce proper cyclin expression, resulting G1 phase arrest, but it unclear whether these are fact secondary decreased B-cell survival, since also affects expression antiapoptotic genes such as bcl-xL. Here, use bcl-xL transgene correct viability c-rel-deficient cells, show that inhibition apoptosis does not necessarily confer hyperproliferation activated BCR. still fail enter S phase despite improved survival by overexpression, suggesting c-Rel-associated dependent on more than just enhanced viability. Overexpression E protein, however, can cooperate Bcl-xL restore via induction cyclin–CDK/Rb–E2F pathway. Furthermore, c-Rel directly regulate transcription e2f3a promoter/enhancer, which then likely lead transcriptional activation promoter E2F3a. Hence, studies provide clear evidence control lymphocyte linked a cyclin-dependent process, suggest only activates progression.