title: Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity.
abstract: As a critical apoptosis executioner, caspase-3 becomes activated and then enters into the nucleus to exert its function. However, the molecular mechanism of this nuclear entry of active caspase-3 is still unknown. In this study, we revealed that caspase-3 harbors a crm-1-independent nuclear export signal (NES) in its small subunit. Using reverse-caspase-3 as the study model, we found that the function of the NES in caspase-3 was not disturbed by the conformational changes during induced caspase-3 activation. Mutations disrupting the cleavage activity or p3-recognition site resulted in a defect in the nuclear entry of active caspase-3. We provide evidence that the p3-mediated specific cleavage activity of active caspase-3 abrogated the function of the NES. In conclusion, our results demonstrate that during caspase-3 activation, NES is constitutively present. p3-mediated specific cleavage activity abrogates the NES function in caspase-3, thus facilitating the nuclear entry of active caspase-3.
authors.affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lu
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.forename: Kehu
authors.initials: K
authors.lastname: Yuan
authors.forename: Quancang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sha
authors.initials: S
authors.lastname: Meng
authors.forename: Fangxun
authors.initials: F
authors.lastname: Wang
authors.forename: Hongchun
authors.initials: H
authors.lastname: Guo
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ju
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Zhonghe
authors.initials: Z
authors.lastname: Zhai
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D053148:Caspase 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004789:Enzyme Activation / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008954:Models, Biological; D049790:Nuclear Export Signals / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000502:physiology; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D053148:Caspase 3; D028884:Karyopherins; D049790:Nuclear Export Signals; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein