View source for ZBTB32

{{Use dmy dates|date=April 2016}}
{{Infobox_gene}}

'''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 cell|T]] and [[B cell]]s upon activation, but also significantly in testis cells. It is a member of the '''Po'''xviruses and Zinc-finger (POZ) and '''K'''rüppel (POK) family of proteins,<ref name="pmid10572087">{{cite journal | vauthors = Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD | title = A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF | journal = Blood | volume = 94 | issue = 11 | pages = 3737–47 | date = December 1999 | pmid = 10572087 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ZBTB32 zinc finger and BTB domain containing 32| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27033 }}</ref> 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.<ref name="Yoon_2012" /> ZBTB32 recruits corepressors, such as [[N-CoR]] and [[HDAC]]s to its target genes, induces repressive chromatin states and acts cooperatively with other proteins, e.g. with [[PRDM1|Blimp-1]],<ref name="Yoon_2012" /> to suppress the transcription of genes .<ref name="Yoon_2012">{{cite journal | vauthors = Yoon HS, Scharer CD, Majumder P, Davis CW, Butler R, Zinzow-Kramer W, Skountzou I, Koutsonanos DG, Ahmed R, Boss JM | title = ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during B cell differentiation to plasma cells | journal = Journal of Immunology | volume = 189 | issue = 5 | pages = 2393–403 | year = 2012 | pmid = 22851713 | pmc = 3424359 | doi = 10.4049/jimmunol.1103371 }}</ref>

It contains a N-terminal [[BTB/POZ domain]] (IPR000210) or a SKP1/BTB/POZ domain (IPR011333), and three C-terminal [[zinc finger]]s, Znf_C2H2_sf. (IPR036236),  Znf_C2H2_type domain (IPR013087), a Znf_RING/FYVE/PHD domain (IPR013083), followed by a putative UBZ4 domain.<ref name="pmid25162118">{{cite journal | vauthors = Rizzo AA, Salerno PE, Bezsonova I, Korzhnev DM  | title = 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 | journal = Biochemistry | volume = 53 | issue = 37 | pages = 5895–906 | date = September 2014 | pmid = 25162118 }}</ref>

== 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),
* PLZF (Promyelocytic Leukemia Zinc Finger and Zbtb16)-like zinc finger protein (PLZP)

== Interactions ==

Zbtb32 has been shown to [[Protein–protein interaction|interact]] with:
* Fanconi anemia complementation group C (Fancc)<ref name = autogenerated1>{{cite journal | vauthors = Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD | title = A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF | journal = Blood | volume = 94 | issue = 11 | pages = 3737–47 | date = December 1999 | pmid = 10572087 | doi =  }}</ref><ref name = pmid14499622>{{cite journal | vauthors = Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA | title = Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport | journal = Experimental Cell Research | volume = 289 | issue = 2 | pages = 211–21 | date = October 2003 | pmid = 14499622 | doi =  10.1016/s0014-4827(03)00261-1}}</ref> 
* Thioredoxin interacting protein (Txnip), but the interaction might be unspecific; however, Vitamin D3 upregulated protein 1 (VDUP1) seems to interact,<ref name = pmid12821938>{{cite journal | vauthors = 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 | title = VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression | journal = Oncogene | volume = 22 | issue = 26 | pages = 4035–46 | date = June 2003 | pmid = 12821938 | doi = 10.1038/sj.onc.1206610 }}</ref> and
* Zinc finger and BTB domain-containing protein 16 (Zbtb16)<ref name = pmid10572087/>
* Zinc-finger elbow-related proline domain protein 2 (Zpo2).<ref name="pmid28258171">{{cite journal | vauthors = Shahi P, Wang CY, Lawson DA, Slorach EM, Lu A, Yu Y, Lai MD, Gonzalez Velozo H, Werb Z | title = ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression | journal = Proc Natl Acad Sci U S A | volume = 114 | issue = 12 | pages = 3169–3174 | date = 2017 | pmid =  28258171 | doi = 10.1073/pnas.1701690114 }}</ref>
* GATA binding protein (Gata2)<ref name = pmid11964310>{{cite journal | vauthors = Tsuzuki S, Enver T | title = 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 | journal = Blood | volume = 99 | issue = 9 | pages = 3404–10 | date = May 2002 | pmid = 11964310 | doi = 10.1182/blood.V99.9.3404 }}</ref>

== Immune system ==

The expression of ZBTB32 is induced by [[inflammatory cytokine]]s and promotes proliferation of [[natural killer]] cells.<ref name="pmid26324348">{{cite journal | vauthors = Beaulieu AM, Madera S, Sun JC | title = Molecular Programming of Immunological Memory in Natural Killer Cells | journal = Advances in Experimental Medicine and Biology | volume = 850 | issue = | pages = 81–91 | date = 2015 | pmid = 26324348 | doi = 10.1007/978-3-319-15774-0_7 | url = }}</ref>

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.<ref name="pmid29707204">{{cite journal | vauthors = Coley WD, Zhao Y, Benck CJ, Liu Y, Hotta-Iwamura C, Rahman MJ, Tarbell KV | title = Loss of Zbtb32 in NOD mice does not significantly alter T cell responses | journal = F1000Research | volume = 7 | issue = | pages = 318 | date = 2018 | pmid = 29707204 | pmc = 5909056 | doi = 10.12688/f1000research.13864.1 }}</ref>

== 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.<ref name="Zhu">{{cite journal | vauthors = Zhu C, Chen G, Zhao Y, Gao XM, Wang J | title = Regulation of the Development and Function of B Cells by ZBTB Transcription Factors | journal = Frontiers in Immunology | volume = 9 | issue = | pages = 580 | date = 2018 | pmid = 29616049 | pmc = 5869932 | doi = 10.3389/fimmu.2018.00580 }}</ref>

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.<ref name="pmid28258171"/>

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''.<ref name="pmid25774687">{{cite journal | vauthors = Zhang C, Zhao H, Li J, Liu H, Wang F, Wei Y, Su J, Zhang D, Liu T, Zhang Y | title = The identification of specific methylation patterns across different cancers | journal = PLoS One | volume = 10| issue = 3 | pages = e0120361 | date = 2015 | pmid =  25774687 | doi = 10.1371/journal.pone.0120361}}</ref>

The expression of Zbtb32 is upregulated after exposure to [[cisplatin]].<ref name="Sourisseau_2016">{{cite journal | vauthors = Sourisseau T, Helissey C, Lefebvre C, Ponsonnailles F, Malka-Mahieu H, Olaussen KA, André F, Vagner S, Soria JC | title = Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance | journal = Cell Cycle | volume = 15 | issue = 2 | pages = 295–302 | date = 2016 | pmid = 26825230 | pmc = 4825832 | doi = 10.1080/15384101.2015.1120918 }}</ref>
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== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Lin W, Lai CH, Tang CJ, Huang CJ, Tang TK | title = Identification and gene structure of a novel human PLZF-related transcription factor gene, TZFP | journal = Biochemical and Biophysical Research Communications | volume = 264 | issue = 3 | pages = 789–95 | date = November 1999 | pmid = 10544010 | doi = 10.1006/bbrc.1999.1594 }}
* {{cite journal | vauthors = Dai MS, Chevallier N, Stone S, Heinrich MC, McConnell M, Reuter T, Broxmeyer HE, Licht JD, Lu L, Hoatlin ME | title = The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific | journal = The Journal of Biological Chemistry | volume = 277 | issue = 29 | pages = 26327–34 | date = July 2002 | pmid = 11986317 | doi = 10.1074/jbc.M201834200 }}
* {{cite journal | vauthors = 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 | title = VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression | journal = Oncogene | volume = 22 | issue = 26 | pages = 4035–46 | date = June 2003 | pmid = 12821938 | doi = 10.1038/sj.onc.1206610 }}
* {{cite journal | vauthors = Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA | title = Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport | journal = Experimental Cell Research | volume = 289 | issue = 2 | pages = 211–21 | date = October 2003 | pmid = 14499622 | doi = 10.1016/S0014-4827(03)00261-1 }}
* {{cite journal|authorlink30=Huda Zoghbi | vauthors = 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 | title = Towards a proteome-scale map of the human protein–protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
* {{cite journal | vauthors = 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 | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | date = May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 }}
* {{cite journal | vauthors = Ikeda R, Yoshida K, Inoue I | title = Identification of FAZF as a novel BMP2-induced transcription factor during osteoblastic differentiation | journal = Journal of Cellular Biochemistry | volume = 101 | issue = 1 | pages = 147–54 | date = May 2007 | pmid = 17171645 | doi = 10.1002/jcb.21165 }}
{{refend}}

== External links ==
* {{MeshName|ZBTB32+protein,+human}}

{{NLM content}}
{{Transcription factors|g2}}

[[Category:Transcription factors]]