Decreased stress inducibility of the HSP68 protein in a rat hepatoma variant clone.
Analysis of the stress response of closely related rat hepatoma clones revealed that the major inducible heat-shock protein 68 (HSP68) was only slightly inducible upon stress in the glucocorticoid-resistant, dedifferentiated clone-2 cells, but strongly activated in the differentiated, glucocorticoid-sensitive Faza 967 cells from which clone 2 was derived. The decreased inducibility of HSP68 in clone-2 cells was not the consequence of altered kinetics of protein synthesis recovery, was not correlated with the deficient inducibility of other major heat-shock proteins and had no effect on the heat sensitivity of the cells. This deficiency was observed after treatment with mild and strong heat and various chemicals. The results of nuclear run-on experiments suggested that the impairment of HSP68 mRNA induction most likely occurs at the transcriptional level and is probably specific for the corresponding gene. In Faza 967 and clone-2 cells, stress activated comparable levels of heat-shock-factor binding to the heat-shock element, and the expression of a reporter gene under the control of murine HSP70.1 promoter was strongly stimulated in both cells. Therefore, our results raise the possibility that the deficient stress inducibility of HSP68 is due to some specific regulation of the endogeneous HSP68 gene, rather than to a deficiency of the heat-shock factor or mutation of the corresponding gene.
Pirity
M
M
Institute of Genetics, Hungarian Academy of Sciences, Szeged.
Nguyen
V T
VT
Dubois
M F
MF
Bensaude
O
O
Hevér-Szabó
A
A
Venetianer
A
A
D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D018053:Arsenites; D001483:Base Sequence; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006358:Hot Temperature; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017670:Sodium Compounds; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D018053:Arsenites; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017670:Sodium Compounds; C017947:sodium arsenite; D001151:Arsenic