ZBTB32
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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
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Further reading
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External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.