CASP6
Каспаза-6 — это белок, который кодируется геном CASP6. Участвует в активации каскада каспаз, ответственных за апоптоз. Расщепляет поли(АДФ-рибозу) полимеразу in vitro, а также ламины. Сверхэкспрессия способствует запрограммированной гибели клеток.
The CASP6 gene encodes caspase-6, an effector caspase that is responsible for apoptosis execution. Caspase-6 is expressed as a dimeric zymogen containing a short prodomain, a large subunit carrying the Cys 163 catalytic cysteine (p20), a small subunit (p10), and an inter‐subunit linker. Although caspase-6 respectively shares partial sequence similarity with caspase-3 and caspase-7, it has several distinctive features. The substrate specificity of caspase-6 is similar to the initiators such as caspase-8 and caspase-9 rather than that of caspase-3 and caspase-7. The pro-domain of caspase-6 inhibits its self-activation in vivo and in vitro. Caspase-6 is activated by proteolytic processing at the prodomain Asp 23, and both sides of the intersubunit linker Asp 179 (caspase-3 cleavage) and Asp 193 (self-activated cleavage). Caspase-6 is often activated by caspase-3 rather than initiator caspases during apoptosis, but it can also be activated in the absence of caspase-3 activity. When stimulated by caspase-1, caspase-6 is also associated with the inflammatory pathway. Active caspase-6 is abundant in the neuropathological lesions of Alzheimer's disease, Huntington's disease, and Parkinson's disease. The physiological outcomes in these neurological disorders are influenced through the cleavage of the neuronal substrates by caspase-6, so it is promising to improve neurodegeneration therapy through caspase-6-targeted therapeutics. |
