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J. Biol. Chem., Vol. 259, Issue 16, 10175-10180, Aug, 1984
RA Schmidt, CJ Schneider and JA Glomset
Previous studies have identified several cellular requirements for
mevalonic acid that appear unrelated to cholesterol, dolichol, or
ubiquinone. To search for other products of mevalonic acid that might
account for these requirements we cultured Swiss 3T3 cells in the presence
of mevinolin, an inhibitor of mevalonic acid biosynthesis, then labeled the
cells with exogenous radioactive mevalonic acid. Upon analyzing the
radioactive material formed, we found that 40-50% of it was not extractable
into lipid solvents, and that most of the lipid- insoluble material behaved
like protein when treated with sodium dodecyl sulfate:chloroform:phenol,
RNase, or proteinase K. Further analysis by electrophoresis revealed that
radioactivity was associated with a few specific proteins that had apparent
molecular weights of 13,000-58,000. Control experiments indicated that
authentic radioactive (R)-mevalonic acid was the active precursor. Other
lines of evidence suggested that mevalonate was first converted to an
isoprenoid compound, then covalently incorporated into proteins by way of a
cycloheximide-insensitive mechanism. These results suggest that Swiss 3T3
cells possess novel metabolic products of mevalonic acid metabolism that
are formed by post-translational incorporation of isoprenoids into specific
cell proteins.
Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins
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