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.
Ziegelbauer
J
J
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley 94720, USA.
Shan
B
B
Yager
D
D
Larabell
C
C
Hoffmann
B
B
Tjian
R
R
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000814:Aniline Compounds / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D015151:Immunoblotting; D039421:Integrin alpha2; D051741:Kruppel-Like Transcription Factors; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D000814:Aniline Compounds; D015703:Antigens, CD; D004268:DNA-Binding Proteins; D039421:Integrin alpha2; D051741:Kruppel-Like Transcription Factors; D016271:Proto-Oncogene Proteins c-myc; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D013449:Sulfonamides; C436947:T 113242; D014157:Transcription Factors; C107961:ZBTB17 protein, human