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Published on: November 10, 2017
Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells
1Apoptosis Signalling Group, Cancer Research Programme, Institut Municipal d'Investigació Mèdica, Parc de Recerca Biomèdica de Barcelona, Dr. Aiguader, 88. 08003 Barcelona, Spain.
Abstract:
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.
Insights
A novel cyclin, cyclin O, is essential for intrinsic apoptosis in lymphoid cells. Its synthesis triggers programmed cell death via caspase activation, independent of cell cycle or DNA damage responses.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Intrinsic apoptosis pathways are crucial for cellular homeostasis and development.
- Understanding the molecular triggers of apoptosis is key to developing targeted therapies.
Purpose of the Study:
- To identify novel molecular regulators of intrinsic apoptosis in lymphoid cells.
- To elucidate the role of cyclin O in apoptosis induction and its relationship with other cellular processes.
Main Methods:
- Investigated cyclin O synthesis and complex formation with Cdk2 during apoptosis.
- Analyzed cyclin O expression in vivo in mouse thymus and spleen.
- Utilized shRNA to knock down cyclin O expression and assessed apoptosis induction.
- Examined the impact of cyclin O on caspase activation and other cellular pathways.
Main Results:
- Identified de novo synthesis of cyclin O as an early step in intrinsic apoptosis.
- Cyclin O forms active complexes with Cdk2, preceding apoptosis induction.
- Overexpression of cyclin O induces caspase-dependent apoptosis.
- Knockdown of cyclin O inhibits glucocorticoid and DNA damage-induced apoptosis by preventing caspase activation.
- Cyclin O-mediated apoptosis is distinct from CD95 death receptor pathways.
Conclusions:
- Cyclin O plays a critical physiological role in inducing apoptosis in lymphoid cells.
- Cyclin O functions independently of cell cycle, DNA damage checkpoints, or glucocorticoid transcriptional responses.
- Cyclin O represents a novel target for modulating apoptosis in lymphoid malignancies and autoimmune diseases.
Related Concept Videos
The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
Anaphase Promoting Complex
Inhibition of Cdk Activity
Positive Regulator Molecules
Positive Regulator Molecules

