Roti Roti J L, Kampinga H H, Malyapa R S, Wright W D, vanderWaal R P, Xu M
Section of Cancer Biology, Washington University School of Medicine, St Louis, MO, USA.
Cell Stress Chaperones. 1998 Dec;3(4):245-55. doi: 10.1379/1466-1268(1998)003<0245:nmaatf>2.3.co;2.
The nuclear matrix organizes nuclear DNA into operational domains in which DNA is undergoing replication, transcription or is inactive. The proteins of the nuclear matrix are among the most thermal labile proteins in the cell, undergoing denaturation at temperatures as low as 43-45 degrees C, i.e. relevant temperatures for the clinical treatment of cancer. Heat shock-induced protein denaturation results in the aggregation of proteins to the nuclear matrix. Protein aggregation with the nuclear matrix is associated with the disruption of many nuclear matrix-dependent functions (e.g. DNA replication, DNA transcription, hnRNA processing, DNA repair, etc.) and cell death. Heat shock proteins are believed to bind denatured proteins and either prevents aggregation or render aggregates more readily dissociable. While many studies suggest a role for Hsp70 in heat resistance, we have recently found that nuclear localization/delocalization of Hsp70 and its rate of synthesis, but not its amount, correlate with a tumor cell's ability to proliferate at 41.1 degrees C. These results imply that not only is the nuclear matrix a target for the lethal effects of heat, but it also is a target for the protective, chaperoning and/or enhanced recovery effects of heat shock proteins.
核基质将核DNA组织成不同的功能区域，在这些区域中，DNA正在进行复制、转录或处于非活性状态。核基质蛋白是细胞中对热最不稳定的蛋白质之一，在低至43 - 45摄氏度的温度下就会发生变性，而这正是癌症临床治疗中的相关温度。热休克诱导的蛋白质变性会导致蛋白质聚集到核基质上。蛋白质与核基质的聚集与许多依赖核基质的功能（如DNA复制、DNA转录、hnRNA加工、DNA修复等）的破坏以及细胞死亡有关。热休克蛋白被认为可以结合变性蛋白质，要么防止聚集，要么使聚集体更容易解离。虽然许多研究表明Hsp70在耐热性方面发挥作用，但我们最近发现，Hsp70的核定位/去定位及其合成速率，而非其含量，与肿瘤细胞在41.1摄氏度下的增殖能力相关。这些结果表明，核基质不仅是热致死效应的靶点，也是热休克蛋白的保护、伴侣和/或增强恢复效应的靶点。
