ZBTB32

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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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

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.

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, 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]

References[]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000011590 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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. ^ a b c 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. ^ a b 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. ISBN 978-3-319-15773-3. 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. Bibcode:2015PLoSO..1020361Z. 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[]

External links[]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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