Sandox Bay Serrano

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Introduction

Caspases are cysteine-aspartic acid proteases and are key protein facilitators for the faithful execution of apoptosis or programmed cell death. Dysregulation in the apoptotic pathway has been implicated in a variety of diseases such as neurodegeneration, cancer, heart disease and some metabolic disorders. Because of the crucial role of caspases in the the apoptotic pathway, abnormalities in their functions would cause a haywire in the apoptotic cascade and can be deleterious to the cell. Caspases are thus being considered as therapeutic targets in apoptosis-related diseases.

Any apoptotic signal received by the cell causes the activation of initiator caspases (-8 and -9) by associating with another protein platform to form a functional holoenzyme. These initiator caspases then cleaves the executioner caspases -3, -6, -7. Caspase-3 specifically functions to cleave both caspase-6 and -7, which in turn cleave their respective targets to induce cell death. Aside from being able to activate caspase-6 and -7, caspase-3 also regulates caspase-9 activity, operating via feedback loop. These dual action of caspase-3 confers its distinct regulatory mechanisms, resulting a wider extent of effects in the apoptotic cascade.


Structure

Caspase-3 dimer (PDB entry 2h5i)

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Proteopedia Page Contributors and Editors (what is this?)

Banyuhay P. Serrano, Michal Harel

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