Biology:ZBTB32

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


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,[1][2] 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.[3] 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,[3] to suppress the transcription of genes .[3]

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.[4]

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)[5][6]
  • Thioredoxin interacting protein (Txnip), but the interaction might be unspecific; however, Vitamin D3 upregulated protein 1 (VDUP1) seems to interact [7]
  • Zinc finger and BTB domain-containing protein 16 (Zbtb16)[1]
  • Zinc-finger elbow-related proline domain protein 2 (Zpo2)[8]
  • GATA binding protein (Gata2)[9]

Immune system

The expression of ZBTB32 is induced by inflammatory cytokines and promotes proliferation of natural killer cells.[10]

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.[11]

Cancer

ZBTB32 is highly expressed in 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.[12]

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.[8]

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.[13]

The expression of Zbtb32 is upregulated after exposure to cisplatin.[14]

References

  1. ↑ 1.0 1.1 "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood 94 (11): 3737–47. December 1999. doi:10.1182/blood.V94.11.3737. PMID 10572087. 
  2. ↑ "Entrez Gene: ZBTB32 zinc finger and BTB domain containing 32". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27033. 
  3. ↑ 3.0 3.1 3.2 "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. 2012. doi:10.4049/jimmunol.1103371. PMID 22851713. 
  4. ↑ "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. September 2014. doi:10.1021/bi500823h. PMID 25162118. 
  5. ↑ "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood 94 (11): 3737–47. December 1999. doi:10.1182/blood.V94.11.3737. PMID 10572087. 
  6. ↑ "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. October 2003. doi:10.1016/s0014-4827(03)00261-1. PMID 14499622. 
  7. ↑ "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene 22 (26): 4035–46. June 2003. doi:10.1038/sj.onc.1206610. PMID 12821938. 
  8. ↑ 8.0 8.1 "ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression". Proc Natl Acad Sci U S A 114 (12): 3169–3174. 2017. doi:10.1073/pnas.1701690114. PMID 28258171. Bibcode: 2017PNAS..114.3169S. 
  9. ↑ "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. May 2002. doi:10.1182/blood.V99.9.3404. PMID 11964310. 
  10. ↑ "Molecular Programming of Immunological Memory in Natural Killer Cells". Crossroads Between Innate and Adaptive Immunity V. Advances in Experimental Medicine and Biology. 850. 2015. pp. 81–91. doi:10.1007/978-3-319-15774-0_7. ISBN 978-3-319-15773-3. 
  11. ↑ "Loss of Zbtb32 in NOD mice does not significantly alter T cell responses". F1000Research 7: 318. 2018. doi:10.12688/f1000research.13864.1. PMID 29707204. 
  12. ↑ "Regulation of the Development and Function of B Cells by ZBTB Transcription Factors". Frontiers in Immunology 9: 580. 2018. doi:10.3389/fimmu.2018.00580. PMID 29616049. 
  13. ↑ "The identification of specific methylation patterns across different cancers". PLOS ONE 10 (3): e0120361. 2015. doi:10.1371/journal.pone.0120361. PMID 25774687. Bibcode: 2015PLoSO..1020361Z. 
  14. ↑ "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. 2016. doi:10.1080/15384101.2015.1120918. PMID 26825230. 

Further reading

  • "Identification and gene structure of a novel human PLZF-related transcription factor gene, TZFP". Biochemical and Biophysical Research Communications 264 (3): 789–95. November 1999. doi:10.1006/bbrc.1999.1594. PMID 10544010. 
  • "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. July 2002. doi:10.1074/jbc.M201834200. PMID 11986317. 
  • "VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression". Oncogene 22 (26): 4035–46. June 2003. doi:10.1038/sj.onc.1206610. PMID 12821938. 
  • "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. October 2003. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622. 
  • "Towards a proteome-scale map of the human protein–protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 
  • "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. May 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569. 
  • "Identification of FAZF as a novel BMP2-induced transcription factor during osteoblastic differentiation". Journal of Cellular Biochemistry 101 (1): 147–54. May 2007. doi:10.1002/jcb.21165. PMID 17171645. 

External links

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



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