Nuclear matrix as a target for hyperthermic killing of cancer cells

JLR Roti*, HH Kampinga, RS Malyapa, WD Wright, RP vanderWaal

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    99 Citations (Scopus)

    Abstract

    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 tu mor 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.

    Original languageEnglish
    Pages (from-to)245-255
    Number of pages11
    JournalCell stress & chaperones
    Volume3
    Issue number4
    Publication statusPublished - Dec-1998

    Keywords

    • THERMOTOLERANT HELA-CELLS
    • HEAT-SHOCKED CELLS
    • PROTEIN-CONTENT
    • RADIATION SENSITIVITY
    • ELECTRON-MICROSCOPY
    • MAMMALIAN-CELLS
    • S3 CELLS
    • DNA
    • CHROMATIN
    • EXPRESSION

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