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Published on: March 5, 2018
Sox11 Reduces Caspase-6 Cleavage and Activity
Elaine Waldron-Roby1, Janine Hoerauf1, Nicolas Arbez1
1Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD, 21287, United States of America.
Abstract:
The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP) family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS) all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.
Insights
Sox11 regulates caspase-6 activity, a key protein in apoptosis. This study identifies Sox11 as a novel caspase-6 regulator, impacting cell death pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis is a crucial cellular process regulated by caspases.
- While many caspases have known regulators like Inhibitors of Apoptosis Proteins (IAPs), caspase-6 regulation remains poorly understood.
- Identifying novel regulators of caspase-6 is essential for understanding its role in cellular events.
Purpose of the Study:
- To identify novel proteins that interact with and regulate caspase-6 activity.
- To investigate the functional impact of Sox11 on caspase-6 and other effector caspases.
- To explore the potential of Sox11 as a therapeutic target in apoptosis-related diseases.
Main Methods:
- Yeast-two-hybrid screening using inactive caspase-6 as bait to identify interacting proteins.
- In vitro assays to assess the effect of Sox11 on caspase-6 activity and self-cleavage.
- Analysis of specific Sox11 regions and nuclear localization signal (NLS) involvement in caspase-6 regulation.
- Testing the impact of Sox11 on other effector and initiator caspases and on cell death.
Main Results:
- Sox11 was identified as a novel caspase-6 interacting protein.
- Sox11 significantly reduced caspase-6 activity and prevented its self-cleavage.
- Specific regions of Sox11, including its NLS, were found to be important for this inhibitory function.
- Sox11 also decreased the activity of other effector caspases and reduced cell death, but not initiator caspases (-8, -9).
- Other Sox proteins showed a lesser ability to reduce caspase-6 activity compared to Sox11.
Conclusions:
- Sox11 is a novel and potent regulator of caspase-6 activity.
- Sox11's ability to inhibit effector caspases suggests a role in controlling apoptosis.
- Further research into Sox11 and its interaction with caspases could reveal new therapeutic strategies for diseases involving dysregulated apoptosis.
Related Concept Videos
01:24Caspases
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway
01:30Apoptosis