Sox11 Reduces Caspase-6 Cleavage and Activity.
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.
Division 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.
Elaine
E
Waldron-Roby
Division 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.
Janine
J
Hoerauf
Division 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.
Nicolas
N
Arbez
Division 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.
Shanshan
S
Zhu
Division 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.
Kirsten
K
Kulcsar
Division 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; Department of Neurology, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD, 21287, United States of America; Department of Pharmacology, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD, 21287, United States of America; Department of Neuroscience, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD, 21287, United States of America; Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD, 21287, United States of America.
Christopher A
CA
Ross
D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins; D053178:Caspase 6 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000096:biosynthesis / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics; D055751:SOXC Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors
D002352:Carrier Proteins; D019913:Nuclear Localization Signals; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D014157:Transcription Factors; D053178:Caspase 6