IDENTIFICATION OF A NOVEL SERINE THREONINE KINASE AND A NOVEL 15-KD PROTEIN AS POTENTIAL MEDIATORS OF THE GAMMA-INTERFERON-INDUCED CELL-DEATH

被引：538

作者：

DEISS, LP ^{[1
]}

FEINSTEIN, E ^{[1
]}

BERISSI, H ^{[1
]}

COHEN, O ^{[1
]}

KIMCHI, A ^{[1
]}

机构：

[1] WEIZMANN INST SCI, DEPT MOLEC GENET & VIROL, IL-76100 REHOVOT, ISRAEL

来源：

GENES & DEVELOPMENT | 1995年 / 9卷 / 01期

关键词：

CELL DEATH; IFN-GAMMA; ANTISENSE CDNA; SERINE THREONINE KINASE;

D O I：

10.1101/gad.9.1.15

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Programmed cell death is often triggered by the interaction of some cytokines with their cell surface receptors. Here, we report that gamma interferon (IEN-gamma) induced in HeLa cells a type of cell death that had cytological characteristics of programmed cell death. In this system we have identified two novel genes whose expression was indispensable for the execution of this type of cell death. The rescue was based on positive growth selection of cells after transfection with antisense cDNA expression libraries. The antisense RNA-mediated inactivation of the two novel genes protected the cells from the IFN-gamma-induced cell death but not from the cytostatic effects of the cytokine or from a necrotic type of cell death. One of those genes (DAP-1) is expressed as a single 2.4-kb mRNA that codes for a basic, proline-rich, 15-kD protein. The second is transcribed into a single 6.3-kb mRNA and codes for a unique 160-kD calmodulin-dependent serine/threonine kinase (DAP kinase) that carries eight ankyrin repeats. The expression levels of the two DAP proteins were selectively reduced by the corresponding antisense RNAs. Altogether, it is suggested that these two novel genes are candidates for positive mediators of programmed cell death that is induced by IFN-gamma.

引用

页码：15 / 30

页数：16

共 61 条

[1] Altschul S.F., Gish W., Miller W., Myers E.W., Lipman D.J., Basic local alignment search tool, J. Mol. Biol., 215, pp. 403-410, (1990)
[2] Askew D.S., Ashmun R.A., Simmons B.C., Cleveland J.L., Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis, Oncogene, 6, pp. 1915-1922, (1991)
[3] Aune T.M., Pogue S.L., Inhibition of tumor cell growth by interferon-gamma is mediated by two distinct mechanisms dependent upon oxygen tension: Induction of tryptophan degradation and depletion of intracellular nicotinamide adenine dinucleotide, J. Clin. Invest., 84, pp. 863-875, (1989)
[4] Blumenthal D.K., Takio K., Edelman A.M., Charbonneau H., Titani K., Walsh K.A., Krebs E.D., Identification of calmodulin-binding domain of skeletal muscle myosin light chain kinase, Proc. Natl. Acad. Sci., 82, pp. 3187-3191, (1985)
[5] Brendel V., Bucher P., Nourbakhsh I.R., Blaisdell B.E., Karlin S., Methods and algorithms for statistical analysis of protein sequences, Proc. Natl. Acad. Sci., 89, pp. 2002-2006, (1992)
[6] Chan T.A., Chu C.A., Rauen K.A., Kroiher M., Tatarewicz S.M., Steele R.E., Identification of a gene encoding a novel protein-tyrosine kinase containing SH2 domains and ankyrin-like repeats, Oncogene, 9, pp. 1253-1259, (1994)
[7] Chomczynski P., Sacchi N., Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction, Anal Biochem., 162, pp. 156-159, (1987)
[8] Clarke A.R., Purdie C.A., Harrison D.J., Morris R.G., Bird C.C., Hooper M.L., Wylie A.H., Thymocyte apoptosis induced by p53-dependant and independent pathways, Nature, 362, pp. 849-852, (1993)
[9] Cohen G.M., Sun X.-M., Snowden R.T., Dinsdale D., Skileter D.N., Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation, Biochem. J., 286, pp. 331-334, (1992)
[10] Cowburn D., Helical encounter, Struct. Biol., 1, pp. 489-491, (1994)

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