Disease relevance of ZBTB17

• Miz-1 binds to start sites of the adenovirus major late and cyclin D1 promoters and activates transcription from both promoters [1].
• In addition, several of the ZNFs mapped to regions implicated in recurrent chromosomal rearrangements in hematological malignancies (ZNF139, 7q21.3-q22.1; ZNF148, 3q21-q22; ZNF151, 1p36.1-p36.2) [2].
• Zinc finger genes mapping to regions commonly deleted in solid tumors included ZNF132, 134, 135, 137, 154, and 155, all located on 19q13 (thyroid adenoma), and ZNF151, at 1p36.1-p36.2 (neuroblastoma, colon cancer, and other tumors) [2].
• The p148h mutation in Msx2 augments the Miz1 effect on Msx2 DNA binding, suggesting a reason why this mutation behaves in vivo as a dominant positive, and providing a potential explanation of the craniosynostosis phenotype [3].
• In addition, the interaction of ECRG1 and Miz-1 could induce expression of P15(INK4b) gene in esophageal cancer 9706 (EC9706) cells [4].

High impact information on ZBTB17

• Recent evidence suggests that complex formation by Myc with a zinc-finger transcription factor, Miz-1, plays an important role in mediating repression by Myc [5].
• BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells [6].
• Our data implicate Miz-1 in a pathway that regulates cell proliferation in response to UV irradiation [7].
• Miz-1 binds to the p21Cip1 core promoter in vivo and is required for upregulation of p21Cip1 upon UV irradiation [7].
• Thus, MIZ-1 appears to be regulated by association with microtubules and may activate gene transcription in response to changes in the cytoskeleton [8].

Biological context of ZBTB17

• Expression of Myc inhibits transactivation, overcomes Miz-1-induced growth arrest and renders Miz-1 insoluble in vivo [1].
• Both cyclin D1 down-regulation and the G(1) slowdown induced by the transposase require Miz-1 [9].
• Through its association with Miz-1, the SB transposase down-regulates cyclin D1 expression in human cells, as evidenced by differential gene expression analysis using microarray hybridization [9].
• A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells [10].
• Protein/protein interaction studies and transient transfection assays demonstrated that HCF-1 interferes with recruitment of p300 to Miz-1, similar to what has been reported with c-Myc [11].

Anatomical context of ZBTB17

• In marked contrast, the ability of c-Myc to induce apoptosis in primary diploid human fibroblasts in response to growth factor withdrawal is entirely dependent on its ability to inactivate Miz-1 [12].
• To study the role of the transcription factor Myc-interacting protein 1 (MIZ-1) in activating various target genes after induction with the microtubule disrupting agent T113242, we have used small interfering RNA duplexes (siRNAs) to knockdown the expression of MIZ-1 [13].
• As expected, depletion of MIZ-1 resulted in the inhibition of T113242-dependent activation of the low-density lipoprotein receptor (LDLR) gene in hepatocytes [13].
• When antisense ECRG1 interdicted expression of endogenous ECRG1 in Balb/c-3T3 cells, Transfection of Miz-1 couldn't induce P15(INK4b) expression [4].

Associations of ZBTB17 with chemical compounds

• MIZ-1 also binds to the promoter and activates transcription of other T113242-induced genes such as alpha(2) integrin [8].

Physical interactions of ZBTB17

• Previous studies showed that ECRG1 overexpression could inhibit cell growth and induce G1 cell cycle arrest and p15(INK4b) expression by interacting with Miz-1 (Myc-interacting zinc finger protein) [14].

Other interactions of ZBTB17

• One mechanism is limited to the binding of Myc-Max heterodimers to the Inr element in their promoters and inhibition of Miz-1 or other transcriptional activators via the C-terminal domain of c-Myc [15].

Analytical, diagnostic and therapeutic context of ZBTB17

• 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 [8].
• Gene expression microarray analysis under various induction conditions identified other T113242-activated genes affected by a decrease in MIZ-1 and inhibition of the ERK pathway [13].
• ECRG1 was co-localized with Miz-1 in nucleus, as shown by confocal microscopy [4].
• The interaction of ECRG1 and Miz-1 was confirmed by glutathione-S-transferase (GST)-pull-down assays in vitro and co-immunoprecipitation experiments in vivo [4].

References