A novel 21-kDa cytochrome c-releasing factor is generated upon treatment of human leukemia U937 cells with geranylgeraniol.
Geranylgeraniol (GGO) induces apoptosis in various lines of human tumor cells through a mitochondrion-dependent pathway. The present study describes identification of a 21-kDa cytochrome c-releasing factor that appears in the cytosolic fraction after treatment of human leukemia U937 cells with GGO. Incubation of isolated mitochondria with a lysate of U937 cells that had been treated with GGO resulted in the release of cytochrome c from the mitochondria. Utilizing this cell-free system, we purified a 21-kDa protein that induced the release of cytochrome c from mitochondria and appeared to be involved in the apoptosis that is induced in U937 cells by GGO. We designated this protein cytochrome c-releasing factor 21 (CRF21). Overexpression of CRF21 in HeLa cells induced the release of cytochrome c from mitochondria, with subsequent apoptosis. Our results suggest that CRF21 might play an important role in the induction of apoptosis by GGO in leukemia U937 cells.
Masuda
Yutaka
Y
Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Maeda
Sayoko
S
Watanabe
Akiko
A
Sano
Yoshihiro
Y
Aiuchi
Toshihiro
T
Nakajo
Shigeo
S
Itabe
Hiroyuki
H
Nakaya
Kazuyasu
K
D000595:Amino Acid Sequence; D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D020298:U937 Cells
D004224:Diterpenes; D024101:Mitochondrial Proteins; D045304:Cytochromes c; C017338:geranylgeraniol