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Expression of IMP dehydrogenase in differentiating HL-60 cells
FR Collart and E Huberman
Biological and Medical Research Division, Argonne National Laboratory, IL
60493-4833.
Addition of mycophenolic acid to cultures of HL-60 cells results in a
decreased cellular level of guanine nucleotides and the induction of cell
differentiation. During the early stages of this induction, steady- state
levels of cellular IMP dehydrogenase (IMPDH), messenger RNA (mRNA), and
protein are increased, perhaps because of cellular compensation for the
inhibition of IMPDH activity. The subsequent decrease in IMPH mRNA and
protein levels after several days of treatment suggests a change in the
control of IMPDH expression. In contrast to the pattern of increased IMPDH
expression observed in the mycophenolic acid-treated cells, treatment of
HL-60 cells with two other inducers of differentiation, namely retinoic
acid and phorbol 12- myristate 13-acetate, resulted in stable or decreased
levels of cellular IMPDH mRNA and protein. However, the kinetics of this
expression were different. These results suggest that a number of factors
influence the regulation of IMPDH expression during the induction of HL-60
cell differentiation, including the nature of the inducer. A decrease in
the cellular IMPDH activity was observed for all of the inducers,
suggesting that this decreased activity may be a determining factor in the
acquisition of a mature phenotype in the HL- 60 cells.
Volume 75,
Issue 3,
pp. 570-576,
02/01/1990
Copyright © 1990 by The American Society of Hematology
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