Zinc finger and BTB domain-containing protein 32 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the 1960 bp ZBTB32

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The 52 kDa protein (487 aa) is a transcriptional

repressor In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...

and the gene is expressed in T and

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s 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, 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. ZBTB32 recruits corepressors, such as N-CoR and

HDAC Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...

s to its target genes, induces repressive chromatin states and acts cooperatively with other proteins, e.g. with

Blimp-1 PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene ''PRDM1'' located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and p ...

, to suppress the transcription of genes . It contains a N-terminal

BTB/POZ domain The BTB/POZ domain is a common structural domain contained within some proteins. The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger proteins and in proteins th ...

(IPR000210) or a SKP1/BTB/POZ domain (IPR011333), and three C-terminal

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...

s, Znf_C2H2_sf. (IPR036236), Znf_C2H2_type domain (IPR013087), a Znf_RING/FYVE/PHD domain (IPR013083), followed by a putative UBZ4 domain.

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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: * Fanconi anemia complementation group C (Fancc) * Thioredoxin interacting protein (Txnip), but the interaction might be unspecific; however, Vitamin D3 upregulated protein 1 (VDUP1) seems to interact * Zinc finger and BTB domain-containing protein 16 (Zbtb16) * Zinc-finger elbow-related proline domain protein 2 (Zpo2) * GATA binding protein (Gata2)

Immune system

The expression of ZBTB32 is induced by

inflammatory cytokine An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include in ...

s and promotes proliferation of

natural killer Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

cells. Zbtb32

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

show a trend to develop

type 1 diabetes Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

, although the difference is not statistically different. Furthermore the Zbtb32 do not show a difference in

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

proliferation, possibly due to compensation from other genes.

Cancer

ZBTB32 is highly expressed in spermatogonial stem cells, in hematopoietic stem and progenitor cells, in

diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibody, antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual Incidence (epidemiology), in ...

(DLBCL) and appears to suppress the immune system by silencing the

CIITA CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and ca ...

gene. 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. 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''. The expression of Zbtb32 is upregulated after exposure to

cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...

References

External links