Validation of the Intermolecular Disulfide Bond in Caspase-2

• Published in: Biology (Basel, Switzerland) Vol. 13; no. 1; p. 49
• Main Authors: Amason, Megan E, Li, Lupeng, Harvest, Carissa K, Lacey, Carolyn A, Miao, Edward A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024
• Subjects: Analysis; Apoptosis; Caspase-2; Cell cycle; Cell death; Chemical bonds; Crystal structure; Cytosol; Dimerization; Disulfide bonds; Enzymatic activity; Enzymes; Ethylenediaminetetraacetic acid; Ferroptosis; Homeostasis; Localization; Medical research; Medicine, Experimental; oxidative damage; Phenotypes; Proteins; United States > US; disulfide bonds; apoptosis; oxidative damage; ferroptosis; caspase-2
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology13010049

Caspases are a family of proteins involved in cell death. Although several caspase members have been well characterized, caspase-2 remains enigmatic. Caspase-2 has been implicated in several phenotypes, but there has been no consensus in the field about its upstream activating signals or its downstream protein targets. In addition, the unique ability of caspase-2 to form a disulfide-bonded dimer has not been studied in depth. Herein, we investigate the disulfide bond in the context of inducible dimerization, showing that disulfide bond formation is dimerization dependent. We also explore and review several stimuli published in the caspase-2 field, test ferroptosis-inducing stimuli, and study in vivo infection models. We hypothesize that the disulfide bond will ultimately prove to be essential for the evolved function of caspase-2. Proving this will require the discovery of cell death phenotypes where caspase-2 is definitively essential.