Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity.
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.
Luo
Min
M
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
Lu
Zhiyong
Z
Sun
He
H
Yuan
Kehu
K
Zhang
Quancang
Q
Meng
Sha
S
Wang
Fangxun
F
Guo
Hongchun
H
Ju
Xiaofang
X
Liu
Yuqing
Y
Ye
Tao
T
Lu
Zhigang
Z
Zhai
Zhonghe
Z
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
D053148:Caspase 3; D028884:Karyopherins; D049790:Nuclear Export Signals; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein