Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells
Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells
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DOI:
10.1038/cdd.2008.145
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发表时间:
2009-02-01
影响因子:
12.4
通讯作者:
Gil-Gomez, G.
中科院分区:
文献类型:
--
作者:
Roig, M. B.;Roset, R.;Gil-Gomez, G.
We have identified an early step common to pathways activated by different forms of intrinsic apoptosis stimuli. It requires de novo synthesis of a novel cyclin, cyclin O, that forms active complexes primarily with Cdk2 upon apoptosis induction in lymphoid cells. Cyclin O expression precedes glucocorticoid and gamma-radiation-induced apoptosis in vivo in mouse thymus and spleen, and its overexpression induces caspase-dependent apoptosis in cultured cells. Knocking down the endogenous expression of cyclin O by shRNA leads to the inhibition of glucocorticoid and DNA damage-induced apoptosis due to a failure in the activation of apical caspases while leaving CD95 death receptor-mediated apoptosis intact. Our data demonstrate that apoptosis induction in lymphoid cells is one of the physiological roles of cyclin O and it does not act by perturbing a normal cellular process such as the cell cycle, the DNA damage checkpoints or transcriptional response to glucocorticoids.