title: Engineering a photoactivated caspase-7 for rapid induction of apoptosis.
abstract: Apoptosis is a cell death program involved in the development of multicellular organisms, immunity, and pathologies ranging from cancer to HIV/AIDS. We present an engineered protein that causes rapid apoptosis of targeted cells in monolayer culture after stimulation with blue light. Cells transfected with the protein switch L57V, a tandem fusion of the light-sensing LOV2 domain and the apoptosis-executing domain from caspase-7, rapidly undergo apoptosis within 60 min after light stimulation. Constant illumination of under 5 min or oscillating with 1 min exposure had no effect, suggesting that cells have natural tolerance to a short duration of caspase-7 activity. Furthermore, the overexpression of Bcl-2 prevented L57V-mediated apoptosis, suggesting that although caspase-7 activation is sufficient to start apoptosis, it requires mitochondrial contribution to fully commit.
authors: Evan
authors: E
authors: Mills
authors: Xi
authors: X
authors: Chen
authors: Elizabeth
authors: E
authors: Pham
authors: Stanley
authors: S
authors: Wong
authors: Kevin
authors: K
authors: Truong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D019556:COS Cells; D053179:Caspase 7 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D055668:Photochemical Processes; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058615:Synthetic Biology; D014162:Transfection
chemical_list: D011993:Recombinant Fusion Proteins; D053179:Caspase 7