INHIBITION OF THE GTP-DEPENDENT POLYMERIZATION OF TUBULIN BY METHYL-3,5-DIIODO-4-(4'-METHOXYPHENOXY) BENZOATE (DIME)

The hormonally inactive thyroid hormone analog methyl-3,5-diiodo-4-(4' -methoxyphenoxy) benzoate (DIME) at 1-5 mu M concentrations inhibits t he GTP-dependent polymerization of MTP as determined by an optical tes t. This inhibition is critically dependent on the concentration of GTP . The quantitative correlation between the concentrations of DIME and GTP, under conditions of a linear rat of MTP polymerization, follows M ichaelis-Menten kinetics and the inhibition portrays a 'mixed' type, w here k(m) for GTP and V-max are altered simultaneously. Chemical analo gs of DIME inhibit MTP polymerization parallel to their antitumorigeni c action in vivo. The MTP site is one of the early cellular response s ites of DIME.