Transcription factor MIZ-1 is regulated via microtubule association

Mol Cell. 2001 Aug;8(2):339-49. doi: 10.1016/s1097-2765(01)00313-6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Aniline Compounds / pharmacology
  • Antigens, CD / metabolism
  • Cell Line
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Genes, Reporter / genetics
  • Immunoblotting
  • Integrin alpha2
  • Kruppel-Like Transcription Factors
  • Microscopy, Fluorescence
  • Microtubules / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptors, LDL / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sulfonamides / pharmacology
  • Transcription Factors
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology*

Substances

  • Aniline Compounds
  • Antigens, CD
  • DNA-Binding Proteins
  • Integrin alpha2
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • Receptors, LDL
  • Recombinant Fusion Proteins
  • Sulfonamides
  • T 113242
  • Transcription Factors
  • ZBTB17 protein, human