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通过研究酿酒酵母来探索RAS癌基因的功能。

Exploring the function of RAS oncogenes by studying the yeast Saccharomyces cerevisiae.

作者信息

Toda T, Broek D, Field J, Michaeli T, Cameron S, Nikawa J, Sass P, Birchmeier C, Powers S, Wigler M

机构信息

Cold Spring Harbor Laboratory, New York 11724.

出版信息

Princess Takamatsu Symp. 1986;17:253-60.

PMID:3332013
Abstract

The RAS oncogenes comprise a family of genes found to be activated in perhaps 10-20% of human cancers and which have been highly conserved in evolution. Homologs of the mammalian RAS exist in the yeast Saccharomyces cerevisiae (RAS1 and RAS2). We have shown that human ras proteins can complement the loss of RAS1 and RAS2 proteins in yeast, and hence are functionally homologous. Both human and yeast RAS proteins can stimulate the magnesium and guanine nucleotide-dependent adenylate cyclase activity present in yeast membranes. However, RAS proteins do not appear to stimulate adenylate cyclase in vertebrate cells. Our studies indicate that although RAS proteins are essential controlling elements of adenylate cyclase in yeast, they have other essential functions in that organisms. RAS proteins are themselves probably controlled by growth regulatory proteins.

摘要

RAS癌基因包含一个基因家族,在大约10%-20%的人类癌症中被发现处于激活状态,并且在进化过程中高度保守。哺乳动物RAS的同源物存在于酿酒酵母(RAS1和RAS2)中。我们已经表明,人类ras蛋白可以弥补酵母中RAS1和RAS2蛋白的缺失,因此在功能上是同源的。人类和酵母的RAS蛋白都可以刺激酵母细胞膜中存在的镁和鸟嘌呤核苷酸依赖性腺苷酸环化酶活性。然而,RAS蛋白似乎不会刺激脊椎动物细胞中的腺苷酸环化酶。我们的研究表明,虽然RAS蛋白是酵母中腺苷酸环化酶的必需调控元件,但它们在该生物体中还有其他重要功能。RAS蛋白本身可能受生长调节蛋白的控制。

相似文献

1
Exploring the function of RAS oncogenes by studying the yeast Saccharomyces cerevisiae.通过研究酿酒酵母来探索RAS癌基因的功能。
Princess Takamatsu Symp. 1986;17:253-60.
2
Novel, activated RAS mutations alter protein-protein interactions.新型激活型RAS突变会改变蛋白质-蛋白质相互作用。
Oncogene. 1996 Sep 19;13(6):1209-20.
3
[Ras proteins in Saccharomyces cerevisiae, their partners and their activation].[酿酒酵母中的Ras蛋白、其伙伴及其激活]
C R Seances Soc Biol Fil. 1997;191(2):221-35.
4
Characterization of Saccharomyces cerevisiae Ras1p and chimaeric constructs of Ras proteins reveals the hypervariable region and farnesylation as critical elements in the adenylyl cyclase signaling pathway.酿酒酵母Ras1p及Ras蛋白嵌合构建体的特性揭示了高变区和法尼基化是腺苷酸环化酶信号通路中的关键元件。
Biochemistry. 2003 Dec 23;42(50):14903-12. doi: 10.1021/bi0349928.
5
New activated RAS2 mutations identified in Saccharomyces cerevisiae.在酿酒酵母中鉴定出新型激活型RAS2突变。
Oncogene. 1993 Dec;8(12):3441-5.
6
The ras gene family.ras基因家族。
Cancer Surv. 1986;5(2):275-89.
7
In yeast, RAS proteins are controlling elements of adenylate cyclase.在酵母中,RAS蛋白是腺苷酸环化酶的调控元件。
Cell. 1985 Jan;40(1):27-36. doi: 10.1016/0092-8674(85)90305-8.
8
Biochemical similarity of Schizosaccharomyces pombe ras1 protein with RAS2 protein of Saccharomyces cervisiae.粟酒裂殖酵母ras1蛋白与酿酒酵母RAS2蛋白的生化相似性。
Yeast. 1995 Jul;11(9):801-8. doi: 10.1002/yea.320110902.
9
Mammalian G proteins: models for ras proteins in transmembrane signalling?
Cancer Surv. 1986;5(2):257-74.
10
Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins.野生型和突变型RAS蛋白对酵母腺苷酸环化酶的差异激活作用。
Cell. 1985 Jul;41(3):763-9. doi: 10.1016/s0092-8674(85)80057-x.

引用本文的文献

1
Reconstruction of human genome evolution in yeast: an educational primer for use with "systematic humanization of the yeast cytoskeleton discerns functionally replaceable from divergent human genes".酵母中人类基因组进化的重建:用于“酵母细胞骨架的系统人源化区分功能可替代的与分化的人类基因”的教育入门
Genetics. 2021 Oct 2;219(2). doi: 10.1093/genetics/iyab118.
2
The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and their Role in Human Tumorigenesis.酿酒酵母作为理解RAS蛋白及其在人类肿瘤发生中作用的模型。
Cells. 2018 Feb 19;7(2):14. doi: 10.3390/cells7020014.
3
Ypt/Rab GTPases: principles learned from yeast.
Ypt/Rab 小 G 蛋白:从酵母中获得的原理
Crit Rev Biochem Mol Biol. 2015;50(3):203-11. doi: 10.3109/10409238.2015.1014023. Epub 2015 Feb 23.
4
Ras protein/cAMP-dependent protein kinase signaling is negatively regulated by a deubiquitinating enzyme, Ubp3, in yeast.在酵母中,Ras 蛋白/cAMP 依赖性蛋白激酶信号被去泛素化酶 Ubp3 负调控。
J Biol Chem. 2013 Apr 19;288(16):11358-65. doi: 10.1074/jbc.M112.449751. Epub 2013 Mar 8.