title: Therapeutic potential of HIV protease-activable CASP3.
abstract: Development of a therapeutic application of CASP3/caspase 3/CPP32, an executor of apoptosis, has been challenging because regulation of its activation is complicated. This study aimed to inhibit cancer cell growth and human immunodeficiency virus type 1 (HIV-1) propagation through a CASP3 mutant, CASP3*, activable by HIV-1-encoded aspartate protease. Active CASP3* was delivered to leukemic cells using a protein transduction vehicle, the lentivirus-like nanoparticle (LENA), which should contain thousands of CASP3*-Gag protein molecules and release the activated CASP3* into the target cell cytoplasm. CASP3*-LENA induced apoptosis in various types of leukemic cells. In addition to being effective against leukemic cells, constitutive expression of CASP3* restricted HIV-1 propagation in SUP-T1 cells. The attenuation of HIV-1 replication in SUP-T1/CASP3* cells was attributed to the elimination of HIV-1-infected cells by apoptosis. These data suggest that CASP3* has therapeutic potential against both lymphoid malignancies and HIV-1 infection.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Miyauchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Urano
authors.forename: Mari
authors.initials: M
authors.lastname: Takizawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Ichikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
mesh_terms: D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D017931:DNA Primers; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000378:metabolism*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D053148:Caspase 3; D016333:HIV Protease