Cell Growth & Differentiation, Vol 1, Issue 3 113-117, Copyright © 1990 by American Association of Cancer Research
Transcriptional down-regulation of c-myc expression by protein synthesis-dependent and -independent pathways in a human T lymphoblastic tumor cell line
H Bading and K Moelling
Max-Planck-Institut fuer Molekulare Genetik, Berlin, Federal Republic of Germany.
We show that in the human T lymphoblastic tumor cell line Molt4 c-myc mRNA
and protein expression is down-regulated after exposure to dimethyl
sulfoxide, to phorbol myristate acetate, or to the calcium ionophore
A23187, which raises the intracellular calcium concentration. A block to
RNA elongation is largely responsible for decreased c-myc transcription.
Although negative regulation by dimethyl sulfoxide takes place even when
protein synthesis is inhibited by cycloheximide, the phorbol myristate
acetate effect is blocked to some extent only by cycloheximide. The calcium
ionophore-induced c-myc suppression, however, strictly requires de novo
protein synthesis. Therefore, two different negative regulatory pathways
are involved in c-myc regulation: one which is independent and one which
depends on de novo protein synthesis. The latter one appears to be mediated
by a rapidly calcium-dependent induced gene product.