Microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase prepared from either rat liver or human fibroblasts was shown to be inactivated in vitro by a factor in extracts of cultured human fibroblasts in a reaction requiring ATP or ADP and Mg2+ or Mn2+. The inactivation factor was found in the soluble fraction of fibroblasts extracts and was shown to be heat-labile, nondialyzable, and precipit...