Zinc finger protein 366, also known as DC-SCRIPT (Dendritic cell-specific transcript), 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, res ...
that in humans is encoded by the ''ZNF366''
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 b ...
.
The ZNF366 gene was first identified in a DNA comparison study between 85 kb of ''
Fugu rubripes'' sequence containing 17 genes with its homologous loci in the human draft
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
.
Function
In 2006, DC-SCRIPT was isolated and characterized in human
monocyte-derived dendritic cells (mo-DCs).
DC-SCRIPT contains a DNA-binding domain (11 C
2H
2 zinc (Zn) fingers), flanked by a proline-rich and an acidic region, which can interact with C-terminal-binding protein 1 (CtBP1), a global
corepressor In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, ...
. In the immune system of both
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
and
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
s, DC-SCRIPT was found to be specifically expressed in dendritic cells (DCs).
In COS-1 cells, DC-SCRIPT was shown to interact with the
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
DNA-binding domain (ERDBD) and represses ER activity through the association with RIP140, CtBP and histone deacetylases.
In DCs, DC-SCRIPT was found to be highly expressed in type one conventional DCs (cDC1s) under the control of PU.1. The presence of DC-SCRIPT is important for the cDC1s lineage specification via maintaining Interferon regulatory factor 8 (IRF8) expression. The DC-SCRIPT deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40.
Breast cancer
In 2010, it was shown that DC-SCRIPT can act as a coregulator of multiple nuclear receptors having opposite effects on type I vs type II NRs. DC-SCRIPT is able to repress ER and PR mediated transcription, whereas it can activate transcription mediated by RAR and PPAR. In the same study, it was shown that breast tumor tissue expresses lower levels of DC-SCRIPT than normal breast tissue from the same patient and that DC-SCRIPT mRNA expression is an independent prognostic factor for good survival of
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
patients with estrogen receptor- and/or progesterone receptor-positive tumors.
References
Further reading
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External links
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{{Transcription factors, g2
Transcription factors