The nuclear matrix: a target for heat shock effects and a determinant for stress response.
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.
Roti Roti
J L
JL
Mallinckrodt Institute of Radiology, Radiation Oncology Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
Wright
W D
WD
VanderWaal
R
R
D000818:Animals; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015530:Nuclear Matrix / Q000378:metabolism* / Q000473:pathology / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology