Differential requirement for Caspase 9 in apoptotic pathways in vivo

被引：1151

作者：

Hakem, R

Hakem, A

Duncan, GS

Henderson, JT

Woo, M

Soengas, MS

Elia, A

de la Pompa, JL

Kagi, D

Khoo, W

Potter, J

Yoshida, R

Kaufman, SA

Lowe, SW

Penninger, JM

Mak, TW ^{[1
]}

机构：

[1] Amgen Inst, Toronto, ON M5G 2C1, Canada

[2] Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada

[3] Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada

[4] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada

[5] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[6] Amgen Inc, Thousand Oaks, CA 91320 USA

来源：

CELL | 1998年 / 94卷 / 03期

关键词：

D O I：

10.1016/S0092-8674(00)81477-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutation of Caspase 9 (Casp9) results in embryonic lethality and defective brain development associated with decreased apoptosis. Casp9 (-/-) embryonic stem cells and embryonic fibroblasts are resistant to several apoptotic stimuli, including UV and gamma irradiation. Casp9(-/-) thymocytes are also resistant to dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation or anti-CD95. Resistance to apoptosis is accompanied by retention of the mitochondrial membrane potential in mutant cells. In addition, cytochrome c is translocated to the cytosol of Casp9(-/-) ES cells upon UV stimulation, suggesting that Casp9 acts downstream of cytochrome c. Caspase processing is inhibited in Casp9(-/-) ES cells but not in thymocytes or splenocytes. Comparison of the requirement for Casp9 and Casp3 in different apoptotic settings indicates the existence of at least four different apoptotic pathways in mammalian cells.

引用

页码：339 / 352

页数：14

共 42 条

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