The nuclear matrix: a target for heat shock effects and a determinant for stress response.
The nuclear matrix: a target for heat shock effects and a determinant for stress response.
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DOI：
10.1615/critreveukargeneexpr.v7.i4.30
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发表时间：
1997
影响因子：
1.6
通讯作者：
J. R. Roti Roti-J.-R.-Roti-Roti-7707447;W. D. Wright;R. Vanderwaal
中科院分区：
文献类型：
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作者：
J. R. Roti Roti-J.-R.-Roti-Roti-7707447;W. D. Wright;R. Vanderwaal
核基质将核DNA组织成可操作的DNA结构域，以进行复制、转录和修复。核基质中的蛋白质是细胞中最不稳定的蛋白质之一，在43摄氏度到45摄氏度的温度下发生变性。热休克诱导的蛋白质变性导致蛋白质聚集到核基质上。由于这种聚集，已经观察到多达100个蛋白质变化。蛋白质与核基质的聚集与核基质依赖的DNA复制、DNA转录、hnRNA加工和DNA修复的破坏有关。这些过程的中断会导致细胞死亡。核基质蛋白的变化通过抑制DNA超卷曲能力和抑制与基质相关的DNA的获取来影响这些过程。热休克蛋白被认为与变性蛋白结合，或者阻止聚集，或者使聚集更容易解离。核基质似乎是热休克有害影响的目标，而HSP70起到了保护作用。然而，核基质可能参与了热休克前后HSP70的表达。我们发现了覆盖小鼠HSP70.3启动子区域的热诱导MAR，这意味着HSP70的表达需要改变基质结合。然而，hsp70.1、70.3和hsc70t基因家族被组织为相对于核基质的活性基因。因此，热诱导基因可能有一种独特的依赖于基质的组织。本综述中提出的工作表明，核基质是热致死效应的靶标，也是热休克基因保护性表达的决定因素。
The nuclear matrix organizes nuclear DNA into operational DNA domains for replication, transcription, and repair. The proteins of the nuclear matrix are among the most thermal labile proteins in the cell, undergoing denaturation at 43 degrees C to 45 degrees C. Heat-shock-induced protein denaturation results in the aggregation of proteins to the nuclear matrix. As many as 100 protein changes have been observed as a result of this aggregation. Protein aggregation with the nuclear matrix is associated with the disruption of nuclear matrix-dependent DNA replication, DNA transcription, hnRNA processing, and DNA repair. Disruptions of these processes lead to cell death. Nuclear matrix protein changes affect these processes by inhibiting DNA supercoiling ability and inhibiting the access to matrix-associated DNA. Heat-shock proteins are believed to bind denatured proteins and either prevent aggregation or render aggregates more readily dissociable. The nuclear matrix appears to be a target for the detrimental effects of heat shock and hsp70 serves to protect against such effects. However, the nuclear matrix may be involved in the pre- and post-heat shock expression of hsp70. We have found a heat-inducible MAR covering the promoter region of murine hsp70.3, implying that changes in matrix association are needed for hsp70 expression. However, the hsp70.1, 70.3, and hsc70t gene family is organized as an active gene with respect to the nuclear matrix. Thus, it may be that heat-inducible genes have a unique matrix-dependent organization. The work presented in this review implies that the nuclear matrix is a target for the lethal effects of heat and is also a determinant in the protective expression of heat-shock genes.