Zinc finger and BTB domain-containing protein 16 explained

Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ZBTB16 gene.

Function

This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL)^[1] and physiological roles have been identified in mouse Natural Killer T cells^{[2] [3]} and gamma-delta T cells.^[4] Alternate transcriptional splice variants have been characterized in human.^{[5] [6]}

Interactions

Zinc finger and BTB domain-containing protein 16 has been shown to interact with:

• Angiotensin II receptor type 1,^[7]
• BCL6,^[8]
• BMI1,^[9]
• Calcitriol receptor,^[10]
• FHL2,^[11]
• GATA1,^[12]
• GATA2,^[13]
• HDAC1,
• HDAC4,
• HDAC5,^{[14] [15]}
• HDAC6,^[14]
• Heparin-binding EGF-like growth factor,^{[16] [17]}
• Nuclear receptor co-repressor 2,^{[18] [19] [20]}
• Promyelocytic leukemia protein^[21]
• RUNX1T1,^{[22] [23]}
• Retinoic acid receptor alpha,^[24]
• SIN3A,^{[25] [18]}
• SIN3B,^[26] and
• ZBTB32.^[27]

See also

• Zbtb7

Further reading

• Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A . Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia . The EMBO Journal . 12 . 3 . 1161–7 . 1993 . 8384553 . 413318 . 10.1002/j.1460-2075.1993.tb05757.x .
• Chen SJ, Zelent A, Tong JH, Yu HQ, Wang ZY, Derré J, Berger R, Waxman S, Chen Z . 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 . The Journal of Clinical Investigation . 91 . 5 . 2260–7 . 1993 . 8387545 . 288229 . 10.1172/JCI116453 .
• Reid A, Gould A, Brand N, Cook M, Strutt P, Li J, Licht J, Waxman S, Krumlauf R, Zelent A . Leukemia translocation gene, PLZF, is expressed with a speckled nuclear pattern in early hematopoietic progenitors . Blood . 86 . 12 . 4544–52 . 1995 . 10.1182/blood.V86.12.4544.bloodjournal86124544 . 8541544 . 8 . free .
• Dong S, Zhu J, Reid A, Strutt P, Guidez F, Zhong HJ, Wang ZY, Licht J, Waxman S, Chomienne C, Chen Z, Zelent A, Chen SJ . Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger-retinoic acid receptor-alpha fusion protein . Proceedings of the National Academy of Sciences of the United States of America . 93 . 8 . 3624–9 . 1996 . 8622986 . 39661 . 10.1073/pnas.93.8.3624 . 1996PNAS...93.3624D . 8 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Hong SH, David G, Wong CW, Dejean A, Privalsky ML . SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor α (RARα) and PLZF-RARα oncoproteins associated with acute promyelocytic leukemia . Proceedings of the National Academy of Sciences of the United States of America . 94 . 17 . 9028–33 . 1997 . 9256429 . 23013 . 10.1073/pnas.94.17.9028 . 1997PNAS...94.9028H . free .
• Koken MH, Reid A, Quignon F, Chelbi-Alix MK, Davies JM, Kabarowski JH, Zhu J, Dong S, Chen S, Chen Z, Tan CC, Licht J, Waxman S, de Thé H, Zelent A . Leukemia-associated retinoic acid receptor α fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies . Proceedings of the National Academy of Sciences of the United States of America . 94 . 19 . 10255–60 . 1997 . 9294197 . 23349 . 10.1073/pnas.94.19.10255 . 1997PNAS...9410255K . 8 . free .
• Lin RJ, Nagy L, Inoue S, Shao W, Miller WH, Evans RM . Role of the histone deacetylase complex in acute promyelocytic leukaemia . Nature . 391 . 6669 . 811–4 . 1998 . 9486654 . 10.1038/35895 . 1998Natur.391..811L . 4383951 . free .
• Guidez F, Ivins S, Zhu J, Söderström M, Waxman S, Zelent A . Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia . Blood . 91 . 8 . 2634–42 . 1998 . 9531570 . 10.1182/blood.V91.8.2634.2634_2634_2642 . free .
• David G, Alland L, Hong SH, Wong CW, DePinho RA, Dejean A . Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein . Oncogene . 16 . 19 . 2549–56 . 1998 . 9627120 . 10.1038/sj.onc.1202043 . 655636 .
• Ahmad KF, Engel CK, Privé GG . Crystal structure of the BTB domain from PLZF . Proceedings of the National Academy of Sciences of the United States of America . 95 . 21 . 12123–8 . 1998 . 9770450 . 22795 . 10.1073/pnas.95.21.12123 . 1998PNAS...9512123F . free .
• van Schothorst EM, Prins DE, Baysal BE, Beekman M, Licht JD, Waxman S, Zelent A, Cornelisse CJ, van Ommen GJ, Richard CW, Devilee P . Genomic structure of the human PLZF gene . Gene . 236 . 1 . 21–4 . 1999 . 10433962 . 10.1016/S0378-1119(99)00277-2 . 8 .
• Ball HJ, Melnick A, Shaknovich R, Kohanski RA, Licht JD . The promyelocytic leukemia zinc finger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase . Nucleic Acids Research . 27 . 20 . 4106–13 . 1999 . 10497277 . 148680 . 10.1093/nar/27.20.4106 .
• Zhang T, Xiong H, Kan LX, Zhang CK, Jiao XF, Fu G, Zhang QH, Lu L, Tong JH, Gu BW, Yu M, Liu JX, Licht J, Waxman S, Zelent A, Chen E, Chen SJ . Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene . Proceedings of the National Academy of Sciences of the United States of America . 96 . 20 . 11422–7 . 1999 . 10500192 . 18049 . 10.1073/pnas.96.20.11422 . 1999PNAS...9611422Z . 8 . free .
• Li X, Peng H, Schultz DC, Lopez-Guisa JM, Rauscher FJ, Marmorstein R . Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein . Cancer Research . 59 . 20 . 5275–82 . 1999 . 10537309 .
• Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD . A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF . Blood . 94 . 11 . 3737–47 . 1999 . 10572087 . 8 . 10.1182/blood.V94.11.3737 .
• Melnick AM, Westendorf JJ, Polinger A, Carlile GW, Arai S, Ball HJ, Lutterbach B, Hiebert SW, Licht JD . The ETO Protein Disrupted in t(8;21)-Associated Acute Myeloid Leukemia Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein . Molecular and Cellular Biology . 20 . 6 . 2075–86 . 2000 . 10688654 . 110824 . 10.1128/MCB.20.6.2075-2086.2000 .
• Hyman J, Chen H, Di Fiore PP, De Camilli P, Brunger AT . Epsin 1 Undergoes Nucleocytosolic Shuttling and Its Eps15 Interactor Nh2-Terminal Homology (Enth) Domain, Structurally Similar to Armadillo and Heat Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn2+ Finger Protein (Plzf) . The Journal of Cell Biology . 149 . 3 . 537–46 . 2000 . 10791968 . 2174850 . 10.1083/jcb.149.3.537 .
• Melnick A, Carlile GW, McConnell MJ, Polinger A, Hiebert SW, Licht JD . AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein . Blood . 96 . 12 . 3939–47 . 2000 . 10.1182/blood.V96.12.3939 . 11090081 .
• Beez S, Demmer P, Puccetti E . Targeting the Acute Promyelocytic Leukemia-Associated Fusion Proteins PML/RARα and PLZF/RARα with Interfering Peptides . PLOS ONE . 7 . 11 . e48636 . 2012 . 23152790 . 3494703 . 10.1371/journal.pone.0048636 . 2012PLoSO...748636B . free .
• He LZ, Bhaumik M, Tribioli C, Rego EM, Ivins S, Zelent A, Pandolfi PP . Two critical hits for promyelocytic leukemia . Molecular Cell . 6 . 5 . 1131–41 . 2000 . 11106752 . 10.1016/S1097-2765(00)00111-8 . free .

Notes and References

1. Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A . Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia . The EMBO Journal . 12 . 3 . 1161–7 . 1993 . 8384553 . 413318 . 10.1002/j.1460-2075.1993.tb05757.x .
2. Kovalovsky D, Uche OU, Eladad S, Hobbs RM, Yi W, Alonzo E, Chua K, Eidson M, Kim HJ, Im JS, Pandolfi PP, Sant'Angelo DB . The BTB-zinc finger transcriptional regulator, PLZF, controls the development of iNKT cell effector functions . Nature Immunology . 9 . 9 . 1055–64 . 2008 . 18660811 . 2662733 . 10.1038/ni.1641 . 8 .
3. Savage AK, Constantinides MG, Han J, Picard D, Martin E, Li B, Lantz O, Bendelac A . The transcription factor PLZF (Zbtb16) directs the effector program of the NKT cell lineage . Immunity . 29 . 3 . 391–403 . 2008 . 18703361 . 2613001 . 10.1016/j.immuni.2008.07.011 .
4. Kreslavsky T, Savage AK, Hobbs R, Gounari F, Bronson R, Pereira P, Pandolfi PP, Bendelac A, von Boehmer H . TCR-inducible PLZF transcription factor required for innate phenotype of a subset of γδ T cells with restricted TCR diversity . Proceedings of the National Academy of Sciences of the United States of America . 106 . 30 . 12453–8 . 2009 . 19617548 . 2718370 . 10.1073/pnas.0903895106 . 2009PNAS..10612453K . free .
5. Zhang T, Xiong H, Kan LX, Zhang CK, Jiao XF, Fu G, Zhang QH, Lu L, Tong JH, Gu BW, Yu M, Liu JX, Licht J, Waxman S, Zelent A, Chen E, Chen SJ . Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene . Proceedings of the National Academy of Sciences of the United States of America . 96 . 20 . 11422–7 . 1999 . 10500192 . 18049 . 10.1073/pnas.96.20.11422 . 1999PNAS...9611422Z . 8 . free .
6. Web site: ZBTB16 zinc finger and BTB domain containing 16 . . 4 October 2009 . 10 October 2009.
7. Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price E, Roberts RL, Imboden H, Fitzgerald TG, Gaffney FA, Inagami T . A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy . EMBO J. . 22 . 24 . 6471–82 . 14657020 . 291832 . 10.1093/emboj/cdg637 . 8 . 2003 .
8. Dhordain P, Albagli O, Honore N, Guidez F, Lantoine D, Schmid M, The HD, Zelent A, Koken MH . Colocalization and heteromerization between the two human oncogene POZ/zinc finger proteins, LAZ3 (BCL6) and PLZF . Oncogene . 19 . 54 . 6240–50 . 11175338 . 10.1038/sj.onc.1203976 . 2000 . 23619694 .
9. Barna M, Merghoub T, Costoya JA, Ruggero D, Branford M, Bergia A, Samori B, Pandolfi PP . Plzf mediates transcriptional repression of HoxD gene expression through chromatin remodeling . Dev. Cell . 3 . 4 . 499–510 . 12408802 . 10.1016/s1534-5807(02)00289-7. 2002 . free .
10. Puccetti E, Obradovic D, Beissert T, Bianchini A, Washburn B, Chiaradonna F, Boehrer S, Hoelzer D, Ottmann OG, Pelicci PG, Nervi C, Ruthardt M . AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor . Cancer Res. . 62 . 23 . 7050–8 . 12460926 . 8 . 2002 .
11. McLoughlin P, Ehler E, Carlile G, Licht JD, Schäfer BW . The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein . J. Biol. Chem. . 277 . 40 . 37045–53 . 12145280 . 10.1074/jbc.M203336200 . 2002 . free .
12. Labbaye C, Quaranta MT, Pagliuca A, Militi S, Licht JD, Testa U, Peschle C . PLZF induces megakaryocytic development, activates Tpo receptor expression and interacts with GATA1 protein . Oncogene . 21 . 43 . 6669–79 . 12242665 . 10.1038/sj.onc.1205884 . 2002 . free .
13. Tsuzuki S, Enver T . 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 . Blood . 99 . 9 . 3404–10 . 11964310 . 10.1182/blood.v99.9.3404. 2002 . free .
14. Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, Dejean A, Harel-Bellan A . HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF . Oncogene . 23 . 54 . 8777–84 . 15467736 . 10.1038/sj.onc.1208128 . 2004 . 26092755 .
15. Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S . Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor . J. Biol. Chem. . 277 . 24 . 22045–52 . 11929873 . 10.1074/jbc.M201736200 . 2002 . 19024903 . free .
16. Nanba D, Mammoto A, Hashimoto K, Higashiyama S . Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF . J. Cell Biol. . 163 . 3 . 489–502 . 14597771 . 2173632 . 10.1083/jcb.200303017 . 2003 .
17. Nanba D, Toki F, Higashiyama S . Roles of charged amino acid residues in the cytoplasmic domain of proHB-EGF . Biochem. Biophys. Res. Commun. . 320 . 2 . 376–82 . 15219838 . 10.1016/j.bbrc.2004.05.176 . 2004 .
18. Wong CW, Privalsky ML . Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6 . J. Biol. Chem. . 273 . 42 . 27695–702 . 9765306 . 10.1074/jbc.273.42.27695. 1998 . free .
19. Takahashi S, McConnell MJ, Harigae H, Kaku M, Sasaki T, Melnick AM, Licht JD . The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT . Blood . 103 . 12 . 4650–8 . 14982881 . 10.1182/blood-2003-08-2759 . 2004 . free .
20. Hong SH, David G, Wong CW, Dejean A, Privalsky ML . SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia . Proc. Natl. Acad. Sci. U.S.A. . 94 . 17 . 9028–33 . 9256429 . 23013 . 10.1073/pnas.94.17.9028. 1997 . 1997PNAS...94.9028H . free .
21. Koken MH, Reid A, Quignon F, Chelbi-Alix MK, Davies JM, Kabarowski JH, Zhu J, Dong S, Chen S, Chen Z, Tan CC, Licht J, Waxman S, de Thé H, Zelent A . Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies . Proc. Natl. Acad. Sci. U.S.A. . 94 . 19 . 10255–60 . 9294197 . 23349 . 10.1073/pnas.94.19.10255. 8 . 1997 . 1997PNAS...9410255K . free .
22. Melnick AM, Westendorf JJ, Polinger A, Carlile GW, Arai S, Ball HJ, Lutterbach B, Hiebert SW, Licht JD . The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein . Mol. Cell. Biol. . 20 . 6 . 2075–86 . 10688654 . 110824 . 10.1128/mcb.20.6.2075-2086.2000. 2000 .
23. Melnick A, Carlile GW, McConnell MJ, Polinger A, Hiebert SW, Licht JD . AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein . Blood . 96 . 12 . 3939–47 . 11090081 . 10.1182/blood.V96.12.3939. 2000 .
24. Martin PJ, Delmotte MH, Formstecher P, Lefebvre P . PLZF is a negative regulator of retinoic acid receptor transcriptional activity . Nucl. Recept. . 1 . 1 . 6 . 14521715 . 212040 . 10.1186/1478-1336-1-6 . 2003 . free .
25. Ward JO, McConnell MJ, Carlile GW, Pandolfi PP, Licht JD, Freedman LP . 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 . Blood . 98 . 12 . 3290–300 . 11719366 . 10.1182/blood.v98.12.3290. 2001 . free .
26. David G, Alland L, Hong SH, Wong CW, DePinho RA, Dejean A . Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein . Oncogene . 16 . 19 . 2549–56 . 9627120 . 10.1038/sj.onc.1202043 . 1998 . 655636 .
27. Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD . A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF . Blood . 94 . 11 . 3737–47 . 10572087 . 10.1182/blood.V94.11.3737. 8 . 1999 .