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Gene Review

ZBTB17  -  zinc finger and BTB domain containing 17

Homo sapiens

Synonyms: MIZ-1, MIZ1, Miz-1, Myc-interacting zinc finger protein 1, ZNF151, ...
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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


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


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


  1. An alternative pathway for gene regulation by Myc. Peukert, K., Staller, P., Schneider, A., Carmichael, G., Hänel, F., Eilers, M. EMBO J. (1997) [Pubmed]
  2. Isolation and fine mapping of 16 novel human zinc finger-encoding cDNAs identify putative candidate genes for developmental and malignant disorders. Tommerup, N., Vissing, H. Genomics (1995) [Pubmed]
  3. Miz1, a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA. Wu, L., Wu, H., Ma, L., Sangiorgi, F., Wu, N., Bell, J.R., Lyons, G.E., Maxson, R. Mech. Dev. (1997) [Pubmed]
  4. Induction of G1 cell cycle arrest and P15INK4b expression by ECRG1 through interaction with Miz-1. Zhao, N., Wang, J., Cui, Y., Guo, L., Lu, S.H. J. Cell. Biochem. (2004) [Pubmed]
  5. Transcriptional repression by Myc. Wanzel, M., Herold, S., Eilers, M. Trends Cell Biol. (2003) [Pubmed]
  6. 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. Phan, R.T., Saito, M., Basso, K., Niu, H., Dalla-Favera, R. Nat. Immunol. (2005) [Pubmed]
  7. Negative regulation of the mammalian UV response by Myc through association with Miz-1. Herold, S., Wanzel, M., Beuger, V., Frohme, C., Beul, D., Hillukkala, T., Syvaoja, J., Saluz, H.P., Haenel, F., Eilers, M. Mol. Cell (2002) [Pubmed]
  8. Transcription factor MIZ-1 is regulated via microtubule association. Ziegelbauer, J., Shan, B., Yager, D., Larabell, C., Hoffmann, B., Tjian, R. Mol. Cell (2001) [Pubmed]
  9. Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1. Walisko, O., Izsvák, Z., Szabó, K., Kaufman, C.D., Herold, S., Ivics, Z. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. Sakurai, T., Itoh, K., Higashitsuji, H., Nagao, T., Nonoguchi, K., Chiba, T., Fujita, J. J. Biol. Chem. (2004) [Pubmed]
  11. Host cell factor-1 interacts with and antagonizes transactivation by the cell cycle regulatory factor Miz-1. Piluso, D., Bilan, P., Capone, J.P. J. Biol. Chem. (2002) [Pubmed]
  12. Targeting of Miz-1 is essential for Myc-mediated apoptosis. Patel, J.H., McMahon, S.B. J. Biol. Chem. (2006) [Pubmed]
  13. Myc-interacting protein 1 target gene profile: a link to microtubules, extracellular signal-regulated kinase, and cell growth. Ziegelbauer, J., Wei, J., Tjian, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  14. ECRG1, a novel candidate of tumor suppressor gene in the esophageal carcinoma, triggers a senescent program in NIH3T3 cells. Zhao, N., Huang, G., Guo, L., Lu, S.H. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  15. Mechanisms of c-myc-mediated transcriptional repression of growth arrest genes. Gartel, A.L., Shchors, K. Exp. Cell Res. (2003) [Pubmed]
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