Transcription factor MIZ-1 is regulated via microtubule association.

A synthetic drug, T113242, activates low-density lipoprotein receptor (LDLR) transcription in the presence of sterols. T113242 also covalently binds to beta-tubulin and induces microtubule depolymerization. The myc-interacting zinc finger protein (MIZ-1) associates with microtubules, can bind directly to the LDLR promoter, and can activate LDLR transcription. MIZ-1 also binds to the promoter and activates transcription of other T113242-induced genes such as alpha(2) integrin. Soft X-ray, indirect immunofluorescence, and green fluorescent protein time-lapse microscopy reveal that MIZ-1 is largely cytoplasmic but accumulates in the nuclei of HepG2 cells upon treatment with T113242. Thus, MIZ-1 appears to be regulated by association with microtubules and may activate gene transcription in response to changes in the cytoskeleton.