ZBTB32

Zinc finger and BTB domain-containing protein 32 is a protein that in humans is encoded by the 1960 bp ZBTB32 gene. The 52 kDa protein (487 aa) is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins,[5][6] and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.

ZBTB32
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesZBTB32, FAXF, FAZF, Rog, TZFP, ZNF538, zinc finger and BTB domain containing 32
External IDsOMIM: 605859 MGI: 1891838 HomoloGene: 8661 GeneCards: ZBTB32
Gene location (Human)
Chr.Chromosome 19 (human)[1]
Band19q13.12Start35,704,558 bp[1]
End35,717,038 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

27033

58206

Ensembl

ENSG00000011590

ENSMUSG00000006310

UniProt

Q9Y2Y4

Q9JKD9

RefSeq (mRNA)

NM_014383
NM_001316902
NM_001316903

NM_021397

RefSeq (protein)

NP_001303831
NP_001303832
NP_055198

NP_067372

Location (UCSC)Chr 19: 35.7 – 35.72 MbChr 7: 30.59 – 30.6 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The protein recruits histone modification enzymes to chromatin to affect gene activation.[7] ZBTB32 recruits corepressors, such as N-CoR and HDACs to its target genes, induces repressive chromatin states and acts cooperatively with other proteins, e.g. with Blimp-1,[7] to suppress the transcription of genes .[7]

It contains a N-terminal BTB/POZ domain (IPR000210) or a SKP1/BTB/POZ domain (IPR011333), and three C-terminal zinc fingers, Znf_C2H2_sf. (IPR036236), Znf_C2H2_type domain (IPR013087), a Znf_RING/FYVE/PHD domain (IPR013083), followed by a putative UBZ4 domain.[8]

Nomenclature

Zinc finger and BTB domain-containing protein 32 is also known as:

  • Fanconi Anemia Zinc Finger Protein (FAZF),
  • Testis Zinc Finger Protein (TZFP),
  • FANCC-Interacting Protein (FAXP),
  • Zinc Finger Protein 538 (ZNF538),
  • Repressor of GATA3 (ROG),
  • Promyelocytic Leukemia Zinc Finger and Zbtb16 (PLZF)-like zinc finger protein (PLZP)

Interactions

Zbtb32 has been shown to interact with:

  • Fanconi anemia complementation group C (Fancc)[9][10]
  • Thioredoxin interacting protein (Txnip), but the interaction might be unspecific; however, Vitamin D3 upregulated protein 1 (VDUP1) seems to interact [11]
  • Zinc finger and BTB domain-containing protein 16 (Zbtb16)[5]
  • Zinc-finger elbow-related proline domain protein 2 (Zpo2)[12]
  • GATA binding protein (Gata2)[13]

Immune system

The expression of ZBTB32 is induced by inflammatory cytokines and promotes proliferation of natural killer cells.[14]

Zbtb32 knockout mice show a trend to develop type 1 diabetes, although the difference is not statistically different. Furthermore the Zbtb32 do not show a difference in lymphocyte proliferation, possibly due to compensation from other genes.[15]

Cancer

ZBTB32 is highly expressed spermatogonial stem cells, in hematopoietic stem and progenitor cells (please also refer to the RNA expression pattern to the right), in diffuse large B-cell lymphoma (DLBCL) and appears to suppress the immune system by silencing the CIITA gene.[16]

The transcription factor gene GATA3 is altered in mammary tumors. Down-regulation of GATA3 expression and activity by the Zinc-finger elbow-related proline domain protein 2 (Zpo2), whereas Zbtb32 facilitates Zpo2 targeting to the GATA3 promoter, results in the development of aggressive breast cancers.[12]

A DNA methylation correlation network was built based on the methylation correlation between differentially methylated genes. A survival analysis of candidate biomarkers was performed. One of eight biomarkers and hub genes identified in colon cancer is ZBTB32.[17]

The expression of Zbtb32 is upregulated after exposure to cisplatin.[18]

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References
  1. GRCh38: Ensembl release 89: ENSG00000011590 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000006310 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (December 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. doi:10.1182/blood.V94.11.3737. PMID 10572087.
  6. "Entrez Gene: ZBTB32 zinc finger and BTB domain containing 32".
  7. Yoon HS, Scharer CD, Majumder P, Davis CW, Butler R, Zinzow-Kramer W, Skountzou I, Koutsonanos DG, Ahmed R, Boss JM (2012). "ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during B cell differentiation to plasma cells". Journal of Immunology. 189 (5): 2393–403. doi:10.4049/jimmunol.1103371. PMC 3424359. PMID 22851713.
  8. Rizzo AA, Salerno PE, Bezsonova I, Korzhnev DM (September 2014). "NMR structure of the human Rad18 zinc finger in complex with ubiquitin defines a class of UBZ domains in proteins linked to the DNA damage response". Biochemistry. 53 (37): 5895–906. doi:10.1021/bi500823h. PMID 25162118.
  9. Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (December 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. doi:10.1182/blood.V94.11.3737. PMID 10572087.
  10. Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/s0014-4827(03)00261-1. PMID 14499622.
  11. Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I (June 2003). "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene. 22 (26): 4035–46. doi:10.1038/sj.onc.1206610. PMID 12821938.
  12. Shahi P, Wang CY, Lawson DA, Slorach EM, Lu A, Yu Y, Lai MD, Gonzalez Velozo H, Werb Z (2017). "ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression". Proc Natl Acad Sci U S A. 114 (12): 3169–3174. doi:10.1073/pnas.1701690114. PMC 5373372. PMID 28258171.
  13. Tsuzuki S, Enver T (May 2002). "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. doi:10.1182/blood.V99.9.3404. PMID 11964310.
  14. Beaulieu AM, Madera S, Sun JC (2015). "Molecular Programming of Immunological Memory in Natural Killer Cells". Advances in Experimental Medicine and Biology. 850: 81–91. doi:10.1007/978-3-319-15774-0_7. PMID 26324348.
  15. Coley WD, Zhao Y, Benck CJ, Liu Y, Hotta-Iwamura C, Rahman MJ, Tarbell KV (2018). "Loss of Zbtb32 in NOD mice does not significantly alter T cell responses". F1000Research. 7: 318. doi:10.12688/f1000research.13864.1. PMC 5909056. PMID 29707204.
  16. Zhu C, Chen G, Zhao Y, Gao XM, Wang J (2018). "Regulation of the Development and Function of B Cells by ZBTB Transcription Factors". Frontiers in Immunology. 9: 580. doi:10.3389/fimmu.2018.00580. PMC 5869932. PMID 29616049.
  17. Zhang C, Zhao H, Li J, Liu H, Wang F, Wei Y, Su J, Zhang D, Liu T, Zhang Y (2015). "The identification of specific methylation patterns across different cancers". PLOS ONE. 10 (3): e0120361. doi:10.1371/journal.pone.0120361. PMC 4361543. PMID 25774687.
  18. Sourisseau T, Helissey C, Lefebvre C, Ponsonnailles F, Malka-Mahieu H, Olaussen KA, André F, Vagner S, Soria JC (2016). "Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance". Cell Cycle. 15 (2): 295–302. doi:10.1080/15384101.2015.1120918. PMC 4825832. PMID 26825230.

Further reading
  • Lin W, Lai CH, Tang CJ, Huang CJ, Tang TK (November 1999). "Identification and gene structure of a novel human PLZF-related transcription factor gene, TZFP". Biochemical and Biophysical Research Communications. 264 (3): 789–95. doi:10.1006/bbrc.1999.1594. PMID 10544010.
  • Dai MS, Chevallier N, Stone S, Heinrich MC, McConnell M, Reuter T, Broxmeyer HE, Licht JD, Lu L, Hoatlin ME (July 2002). "The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific". The Journal of Biological Chemistry. 277 (29): 26327–34. doi:10.1074/jbc.M201834200. PMID 11986317.
  • Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I (June 2003). "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene. 22 (26): 4035–46. doi:10.1038/sj.onc.1206610. PMID 12821938.
  • Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein–protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
  • Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
  • Ikeda R, Yoshida K, Inoue I (May 2007). "Identification of FAZF as a novel BMP2-induced transcription factor during osteoblastic differentiation". Journal of Cellular Biochemistry. 101 (1): 147–54. doi:10.1002/jcb.21165. PMID 17171645.

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