Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis.
Nucling is a novel protein isolated from murine embryonal carcinoma cells with an up-regulated expression during cardiac muscle differentiation. We show here that Nucling was up-regulated by proapoptotic stimuli and important for the induction of apoptosis after cytotoxic stress. We further demonstrated that overexpressed Nucling was able to induce apoptosis. In Nucling-deficient cells, the expression levels of Apaf-1 and cytochrome c, which are the major components of an apoptosis-promoting complex named apoptosome, were both down-regulated under cellular stress. A deficiency of Nucling also conferred resistance to apoptotic stress on the cell. After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex, suggesting that Nucling might be a key molecule for the formation and maintenance of this complex. Nucling induced translocation of Apaf-1 to the nucleus, thereby distributing the Nucling/Apaf-1/pro-caspase-9 complex to the nuclear fraction. These findings suggest that Nucling recruits and transports the apoptosome complex during stress-induced apoptosis.
The Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
Takashi
T
Sakai
Li
L
Liu
Xichuan
X
Teng
Rika
R
Mukai-Sakai
Hidenori
H
Shimada
Ryuji
R
Kaji
Tasuku
T
Mitani
Mitsuru
M
Matsumoto
Kazunori
K
Toida
Kazunori
K
Ishimura
Yuji
Y
Shishido
Tak W
TW
Mak
Kiyoshi
K
Fukui
D000483:Alleles; D000590:Amino Acid Chloromethyl Ketones / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D019076:Transgenes; D014466:Ultraviolet Rays; D015854:Up-Regulation
C506592:APAF1 protein, human; D000590:Amino Acid Chloromethyl Ketones; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D011506:Proteins; C483107:Uaca protein, mouse; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D012313:RNA; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases