CASP7
Каспаза-7 является белком, который кодируется геном CASP7. Участвует в активации каскада каспаз, ответственных за апоптоз. Расщепляет и активирует белки, связывающие регуляторные элементы стерола (SREBP). Протеолитически расщепляет поли(АДФ-рибозу) полимеразу (PARP) в связи '216-Asp-|-Gly-217'. Сверхэкспрессия способствует запрограммированной гибели клеток.
Caspase-7, encoded by CASP7, is an executioner caspase that carries out apoptosis by cleaving cellular components. Because of the structural similarity and the conservation of the residues facing the catalytic site between caspase-3 and caspase-7, caspase-7 shows high similarities with caspase-3 in vitro substrate preference and functions. Procaspase-7 is synthesized as a 303-amino acid inactive zymogen that resides in the cytosol as a pre-assembled homodimer. Like other caspases, pro-caspase-7 must be proteolytically processed to be an active protease. The activation of the caspase-7 is stimulated by caspase-9 through proteolytic cleavage at specific internal aspartic acid residues to separate the large and small subunits of the mature caspase. Alternatively, caspase-7 can be activated by caspase-8 through DNA-damage-induced mitochondrial cytochrome c leakage into the cytosol to complex with the adaptor protein Apaf-1 to form the apoptosome. Upon activation, caspase-7 is responsible for the proteolytic degradation of the cellular targets, ultimately leading to apoptosis. Caspase-3 and caspase-7 exhibit almost indistinguishable activity toward certain synthetic peptide substrates, which often makes people believe that these two proteases occupy functionally redundant roles within the cell death machinery. Nevertheless, extensive biochemical studies demonstrated that caspase-3 and caspase-7 perform different activities toward multiple protein substrates, with caspase-7 being more selective. In addition to its activation during apoptosis, pro-caspase-7 is also processed to mature active caspase-7 in inflammatory conditions. Lamkanfi M et al. confirmed that caspase-7 is a direct substrate of caspase-1 with maturation occurring after the canonical activation sites Asp23 and Asp198. |
