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Gene Review

ZBTB16  -  zinc finger and BTB domain containing 16

Homo sapiens

Synonyms: PLZF, Promyelocytic leukemia zinc finger protein, ZNF145, Zinc finger and BTB domain-containing protein 16, Zinc finger protein 145, ...
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Disease relevance of ZBTB16


High impact information on ZBTB16

  • Two rare variants of APL have been described, in which RARA is fused to one of two other genes, PLZF and NPM [6].
  • Mutant forms of RARalpha, created by chromosomal translocations with either the PML (for promyelocytic leukaemia) or the PLZF (for promyelocytic leukaemia zinc finger) locus, are oncogenic and result in human acute promyelocytic leukaemia (APL) [7].
  • PLZF-RARalpha contains a second, RA-resistant binding site in the PLZF amino-terminal region [8].
  • Strikingly, BCoR interacts selectively with the POZ domain of BCL-6 but not with eight other POZ proteins tested, including PLZF [9].
  • Further molecular analysis of this patient showed a rearrangement between the RAR alpha gene and a newly discovered zinc finger gene named PLZF (promyelocytic leukemia zinc finger) [10].

Chemical compound and disease context of ZBTB16


Biological context of ZBTB16


Anatomical context of ZBTB16

  • In transiently transfected cells and in a cell line derived from a patient with t(8;21) leukemia, PLZF and AML-1/ETO formed a tight complex [17].
  • AML-1/ETO also excluded PLZF from the nuclear matrix and reduced its ability to bind to its cognate DNA-binding site [17].
  • The fusion PLZF-RAR alpha gene found in this case, was not found in DNA obtained from the bone marrow of normals, APL with t(15;17) and in one patient with AML-M2 with a t(11;17) [10].
  • These abnormal transactivation properties observed in retinoic acid-sensitive myeloid cells strongly implicate the PLZF-RAR alpha fusion proteins in the molecular pathogenesis of APL [18].
  • In addition, stable, inducible expression of PLZF in U937 cells inhibited the ability of 1,25(OH)(2)D(3) to induce surface expression of the monocytic marker CD14 and morphologic changes associated with differentiation [19].

Associations of ZBTB16 with chemical compounds


Physical interactions of ZBTB16


Co-localisations of ZBTB16


Regulatory relationships of ZBTB16


Other interactions of ZBTB16

  • SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia [22].
  • We found that ETO is one of the corepressors recruited by PLZF [1].
  • This ATRA-insensitive interaction between N-CoR and PLZF-RARalpha was mediated by the N-terminal PLZF moiety of the chimera [27].
  • A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF [24].
  • PLZF, like BCL6, strongly represses transcription initiated from different promoters [3].

Analytical, diagnostic and therapeutic context of ZBTB16


  1. The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein. Melnick, A.M., Westendorf, J.J., Polinger, A., Carlile, G.W., Arai, S., Ball, H.J., Lutterbach, B., Hiebert, S.W., Licht, J.D. Mol. Cell. Biol. (2000) [Pubmed]
  2. Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors. Melnick, A., Carlile, G., Ahmad, K.F., Kiang, C.L., Corcoran, C., Bardwell, V., Prive, G.G., Licht, J.D. Mol. Cell. Biol. (2002) [Pubmed]
  3. Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein. David, G., Alland, L., Hong, S.H., Wong, C.W., DePinho, R.A., Dejean, A. Oncogene (1998) [Pubmed]
  4. Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF. Dhordain, P., Albagli, O., Honore, N., Guidez, F., Lantoine, D., Schmid, M., The, H.D., Zelent, A., Koken, M.H. Oncogene (2000) [Pubmed]
  5. Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling. Ruthardt, M., Testa, U., Nervi, C., Ferrucci, P.F., Grignani, F., Puccetti, E., Grignani, F., Peschle, C., Pelicci, P.G. Mol. Cell. Biol. (1997) [Pubmed]
  6. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Wells, R.A., Catzavelos, C., Kamel-Reid, S. Nat. Genet. (1997) [Pubmed]
  7. Role of the histone deacetylase complex in acute promyelocytic leukaemia. Lin, R.J., Nagy, L., Inoue, S., Shao, W., Miller, W.H., Evans, R.M. Nature (1998) [Pubmed]
  8. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Grignani, F., De Matteis, S., Nervi, C., Tomassoni, L., Gelmetti, V., Cioce, M., Fanelli, M., Ruthardt, M., Ferrara, F.F., Zamir, I., Seiser, C., Grignani, F., Lazar, M.A., Minucci, S., Pelicci, P.G. Nature (1998) [Pubmed]
  9. BCoR, a novel corepressor involved in BCL-6 repression. Huynh, K.D., Fischle, W., Verdin, E., Bardwell, V.J. Genes Dev. (2000) [Pubmed]
  10. Rearrangements of the retinoic acid receptor alpha and promyelocytic leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukemia. Chen, S.J., Zelent, A., Tong, J.H., Yu, H.Q., Wang, Z.Y., Derré, J., Berger, R., Waxman, S., Chen, Z. J. Clin. Invest. (1993) [Pubmed]
  11. Inhibiting estrogen responses in breast cancer cells using a fusion protein encoding estrogen receptor-alpha and the transcriptional repressor PLZF. Buluwela, L., Pike, J., Mazhar, D., Kamalati, T., Hart, S.M., Al-Jehani, R., Yahaya, H., Patel, N., Sarwar, N., Sarwarl, N., Heathcote, D.A., Schwickerath, O., Phoenix, F., Hill, R., Aboagye, E., Shousha, S., Waxman, J., Lemoine, N.R., Zelent, A., Coombes, R.C., Ali, S. Gene Ther. (2005) [Pubmed]
  12. Identification and characterization of PLZF as a prostatic androgen-responsive gene. Jiang, F., Wang, Z. Prostate (2004) [Pubmed]
  13. Deregulated expression of promyelocytic leukemia zinc finger protein in B-cell chronic lymphocytic leukemias does not affect cyclin A expression. Parrado, A., Noguera, M.E., Delmer, A., McKenna, S., Davies, J., Le Gall, I., Bentley, P., Whittaker, J.A., Sigaux, F., Chomienne, C., Padua, R.A. Hematol. J. (2000) [Pubmed]
  14. Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein. Guidez, F., Howell, L., Isalan, M., Cebrat, M., Alani, R.M., Ivins, S., Hormaeche, I., McConnell, M.J., Pierce, S., Cole, P.A., Licht, J., Zelent, A. Mol. Cell. Biol. (2005) [Pubmed]
  15. Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein. Tsuzuki, S., Enver, T. Blood (2002) [Pubmed]
  16. Modification of promyelocytic leukemia zinc finger protein (PLZF) by SUMO-1 conjugation regulates its transcriptional repressor activity. Kang, S.I., Chang, W.J., Cho, S.G., Kim, I.Y. J. Biol. Chem. (2003) [Pubmed]
  17. AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein. Melnick, A., Carlile, G.W., McConnell, M.J., Polinger, A., Hiebert, S.W., Licht, J.D. Blood (2000) [Pubmed]
  18. PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. Chen, Z., Guidez, F., Rousselot, P., Agadir, A., Chen, S.J., Wang, Z.Y., Degos, L., Zelent, A., Waxman, S., Chomienne, C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  19. The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D(3)-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D(3) receptor. Ward, J.O., McConnell, M.J., Carlile, G.W., Pandolfi, P.P., Licht, J.D., Freedman, L.P. Blood (2001) [Pubmed]
  20. Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger-retinoic acid receptor-alpha fusion protein. Dong, S., Zhu, J., Reid, A., Strutt, P., Guidez, F., Zhong, H.J., Wang, Z.Y., Licht, J., Waxman, S., Chomienne, C., Chen, Z., Zelent, A., Chen, S.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT. Takahashi, S., McConnell, M.J., Harigae, H., Kaku, M., Sasaki, T., Melnick, A.M., Licht, J.D. Blood (2004) [Pubmed]
  22. SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia. Hong, S.H., David, G., Wong, C.W., Dejean, A., Privalsky, M.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  23. The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein. McLoughlin, P., Ehler, E., Carlile, G., Licht, J.D., Schäfer, B.W. J. Biol. Chem. (2002) [Pubmed]
  24. A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF. Hoatlin, M.E., Zhi, Y., Ball, H., Silvey, K., Melnick, A., Stone, S., Arai, S., Hawe, N., Owen, G., Zelent, A., Licht, J.D. Blood (1999) [Pubmed]
  25. Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARalpha fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)(q23;q21) APL patient. Koken, M.H., Daniel, M.T., Gianni, M., Zelent, A., Licht, J., Buzyn, A., Minard, P., Degos, L., Varet, B., de Thé, H. Oncogene (1999) [Pubmed]
  26. Current topics in pharmacological research on bone metabolism: Promyelotic leukemia zinc finger (PLZF) and tumor necrosis factor-alpha-stimulated gene 6 (TSG-6) identified by gene expression analysis play roles in the pathogenesis of ossification of the posterior longitudinal ligament. Inoue, I., Ikeda, R., Tsukahara, S. J. Pharmacol. Sci. (2006) [Pubmed]
  27. Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia. Guidez, F., Ivins, S., Zhu, J., Söderström, M., Waxman, S., Zelent, A. Blood (1998) [Pubmed]
  28. The promyelocytic leukemia zinc finger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase. Ball, H.J., Melnick, A., Shaknovich, R., Kohanski, R.A., Licht, J.D. Nucleic Acids Res. (1999) [Pubmed]
  29. Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia. Hummel, J.L., Wells, R.A., Dubé, I.D., Licht, J.D., Kamel-Reid, S. Oncogene (1999) [Pubmed]
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