可溶性透明质酸受体RHAMM通过抑制Cdc2和细胞周期蛋白B1的表达诱导有丝分裂停滞。
Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression.
作者信息
Mohapatra S, Yang X, Wright J A, Turley E A, Greenberg A H
机构信息
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
出版信息
J Exp Med. 1996 Apr 1;183(4):1663-8. doi: 10.1084/jem.183.4.1663.
Abstract
The hyaluronan (HA) receptor RHAMM is an important regulator of cell growth. Overexpression of RHAMM is transforming and is required for H-ras transformation. The molecular mechanism underlying growth control by RHAMM and other extracellular matrix receptors remains largely unknown. We report that soluble RHAMM induces G2/M arrest by suppressing the expression of Cdc2/Cyclin B1, a protein kinase complex essential for mitosis. Down-regulation of RHAMM by use of dominant negative mutants or antisense of mRNA also decreases Cdc2 protein levels. Suppression of Cdc2 occurs as a result of an increased rate of cdc2 mRNA degradation. Moreover, tumor cells treated with soluble RHAMM are unable to form lung metastases. Thus, we show that mitosis is directly linked to RHAMM through control of Cdc2 and Cyclin B1 expression. Failure to sustain levels of Cdc2 and Cyclin B1 proteins leads to cell cycle arrest.
摘要
透明质酸（HA）受体RHAMM是细胞生长的重要调节因子。RHAMM的过表达具有转化作用，并且是H-ras转化所必需的。RHAMM和其他细胞外基质受体调控生长的分子机制在很大程度上仍不清楚。我们报告称，可溶性RHAMM通过抑制Cdc2/细胞周期蛋白B1的表达诱导G2/M期阻滞，Cdc2/细胞周期蛋白B1是一种对有丝分裂至关重要的蛋白激酶复合物。使用显性负性突变体或mRNA反义技术下调RHAMM也会降低Cdc2蛋白水平。Cdc2的抑制是由于cdc2 mRNA降解速率增加所致。此外，用可溶性RHAMM处理的肿瘤细胞无法形成肺转移。因此，我们表明有丝分裂通过控制Cdc2和细胞周期蛋白B1的表达与RHAMM直接相关。无法维持Cdc2和细胞周期蛋白B1蛋白的水平会导致细胞周期阻滞。
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本文引用的文献
1
A cell cycle and mutational analysis of anchorage-independent growth: cell adhesion and TGF-beta 1 control G1/S transit specifically.非锚定依赖生长的细胞周期与突变分析：细胞黏附及转化生长因子β1特异性调控G1/S期转换
J Cell Biol. 1993 Jul;122(2):461-71. doi: 10.1083/jcb.122.2.461.
2
A link between cyclin A expression and adhesion-dependent cell cycle progression.细胞周期蛋白A表达与黏附依赖性细胞周期进程之间的联系。
Science. 1993 Dec 3;262(5139):1572-5. doi: 10.1126/science.8248807.
3
Premature p34cdc2 activation required for apoptosis.细胞凋亡需要过早激活p34cdc2。
Science. 1994 Feb 25;263(5150):1143-5. doi: 10.1126/science.8108732.
4
Integrins and signal transduction pathways: the road taken.整合素与信号转导通路：走过的道路
Science. 1995 Apr 14;268(5208):233-9. doi: 10.1126/science.7716514.
5
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J Cell Biol. 1993 Nov;123(3):749-58. doi: 10.1083/jcb.123.3.749.
6
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7
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8
9
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10
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