Inactivation of Bcl-2 by phosphorylation
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1Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Abstract:
The antiapoptosis potential of Bcl-2 protein is well established, but the mechanism of Bcl-2 action is still poorly understood. Using the phosphatase inhibitor okadaic acid or the chemotherapeutic drug taxol, we found that Bcl-2 was phosphorylated in lymphoid cells. Phospho amino acid analysis revealed that Bcl-2 was phosphorylated on serine. Under similar conditions, okadaic acid or taxol treatment led to the induction of apoptosis in these cells. Thus, phosphorylation of Bcl-2 seems to inhibit its ability to interfere with apoptosis. In addition, phosphorylated Bcl-2 can no longer prevent lipid peroxidation as required to protect cells from apoptosis.
Insights
Phosphorylation of the Bcl-2 protein inhibits its anti-apoptotic function. This phosphorylation prevents Bcl-2 from blocking apoptosis and lipid peroxidation, crucial for cell survival.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The anti-apoptotic function of Bcl-2 protein is recognized, but its precise mechanism remains unclear.
- Understanding Bcl-2's role is crucial for developing therapies targeting cell death pathways.
Purpose of the Study:
- To investigate the mechanism by which Bcl-2 protein inhibits apoptosis.
- To determine the effect of phosphorylation on Bcl-2's anti-apoptotic activity.
Main Methods:
- Lymphoid cells were treated with phosphatase inhibitor okadaic acid or chemotherapeutic drug taxol.
- Phospho amino acid analysis was performed to identify phosphorylation sites.
- Apoptosis induction and lipid peroxidation were assessed under treatment conditions.
Main Results:
- Bcl-2 protein was phosphorylated on serine residues in lymphoid cells upon treatment with okadaic acid or taxol.
- These treatments also induced apoptosis in the cells.
- Phosphorylated Bcl-2 demonstrated an impaired ability to prevent apoptosis and lipid peroxidation.
Conclusions:
- Phosphorylation of Bcl-2 on serine inhibits its anti-apoptotic function.
- This phosphorylation event disrupts Bcl-2's protective mechanisms against apoptosis and lipid peroxidation.
- The findings provide new insights into the regulation of Bcl-2 activity and apoptosis.