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Investigating Structures And Functions Of Apoptotic Caspases, Ishankumar V. Soni
Investigating Structures And Functions Of Apoptotic Caspases, Ishankumar V. Soni
Doctoral Dissertations
Caspases are cysteine aspartate proteases involved in various cellular pathways including apoptosis, inflammation, and neurodegeneration. Caspase-9 is classified as an initiator apoptotic caspase that is activated upon intrinsic stress. Caspase-9 is composed of two domains: an N- terminal CARD domain and a catalytic core domain. We have employed hydrogen deuterium exchange mass spectrometry (H/DX-MS) to determine the 1) dynamics of the full-length caspase- 9, 2) dynamic impacts on caspase-9 upon substrate-induced dimerization, and 3) regions involved in the CARD: catalytic core domains interactions. Upon intrinsic stress, caspase-9 activates executioners, procaspase-3 and -7 but not procaspase-6. We have employed site-directed mutagenesis …
The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano
The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano
Doctoral Dissertations
Caspases are the cysteine proteases that facilitate the fundamental pathway of programmed cell death or apoptosis. The activation and function of these powerful enzymes are tightly regulated to ensure the faithful execution of apoptosis and prevent untimely cell death. Many deadly human diseases such as cancer, neurodegeneration and autoimmune disorders have been associated with defective activation and faulty regulation of caspases. As such, caspases are considered as attractive drug targets, which when properly controlled, can lead to effective therapeutics for apoptosis-related diseases. Thus, comprehensive investigations of the structure, function and regulation of caspases are necessary to understand the complex mechanisms …