Downregulation of c-myc expression after heat shock in human B-cell lines is independent of 5' mRNA sequences.
The effect of heat-shock on the expression of c-myc genes in different chromosomal contexts was investigated in a panel of human B-lymphoid cell lines. Burkitt's lymphoma cell lines with c-myc translocation breakpoints upstream of the first exon, within the exon itself, or in the first intron showed downregulation of c-myc levels as did a cell line without any translocation. The c-myc mRNA of cell lines with translocation breakpoints within the c-myc gene have previously been reported to have prolonged half-lives. After heat shock, the levels of these mRNA species were reduced with similar kinetics as the normal c-myc mRNA. An exception was an RNA species where the only c-myc sequences are derived from exon 1, showing that sequences from this part of the c-myc gene are not sufficient to mediate the rapid downregulation. Nuclear run-on analysis did not show reduced transcription of c-myc after heat shock and a comparison of cytoplasmic and total RNA did not indicate accumulation of longer, unspliced c-myc mRNA species. These observations suggest a posttranscriptional, cytoplasmic downregulation targeting exons 2 and/or 3. B-lymphoma lines transfected with a hsp70 promoter-linked c-myc gene were deficient in their ability to reinitiate proliferation after heat shock, providing a physiological rationale for the normal downregulation of c-myc after this type of physical stress.
Wennborg
A
A
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Classon
M
M
Klein
G
G
von Gabain
A
A
D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D016259:Genes, myc / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D008223:Lymphoma / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger