title: A-kinase-anchoring protein 95 functions as a potential carrier for the nuclear translocation of active caspase 3 through an enzyme-substrate-like association.
abstract: Caspase-mediated proteolysis is a critical and central element of the apoptotic process, and caspase 3, one of the effector caspases, is proposed to play essential roles in the nuclear morphological changes of apoptotic cells. Although many substrates for caspase 3 localize in the nucleus and caspase 3 translocates from the cytoplasm to the nuclei after activation in apoptotic cells, the molecular mechanisms of nuclear translocation of active caspase 3 have been unclear. Recently, we suggested that a substrate-like protein(s) served as a carrier to transport caspase 3 from the cytoplasm into the nucleus. In the present study, we identified A-kinase-anchoring protein 95 (AKAP95) as a caspase 3-binding protein. Small interfering RNA-mediated depletion of AKAP95 reduced apoptotic nuclear morphological changes, suggesting that AKAP95 is involved in the process of apoptotic nuclear morphological changes. The association of AKAP95 with active caspase 3 was analogous to an enzyme-substrate interaction. Furthermore, overexpression of AKAP95 with nuclear localization sequence mutations inhibited nuclear morphological changes in apoptotic cells. These results indicate that AKAP95 is a potential carrier protein for active caspase 3 from the cytoplasm into the nuclei in apoptotic cells.
authors.affiliation: Molecular and Cell Biology Laboratory, The Salk Institute, La Jolla, CA, USA. skamada@kobe-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamada
authors.forename: Ushio
authors.initials: U
authors.lastname: Kikkawa
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Tsujimoto
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
mesh_terms: D054758:A Kinase Anchor Proteins; D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
chemical_list: D054758:A Kinase Anchor Proteins; C485099:AKAP8 protein, human; D048868:Adaptor Proteins, Signal Transducing; D019913:Nuclear Localization Signals; D011506:Proteins; D034741:RNA, Small Interfering; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases