ZNF366

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Zinc finger protein 366, also known as DC-SCRIPT (Dendritic cell-specific transcript), is a protein that in humans is encoded by the ZNF366 gene.{{cite web | title = Entrez Gene: ZNF366 zinc finger protein 366| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=167465}} 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.{{cite journal | vauthors = Gilligan P, Brenner S, Venkatesh B | title = Fugu and human sequence comparison identifies novel human genes and conserved non-coding sequences | journal = Gene | volume = 294 | issue = 1–2 | pages = 35–44 | date = July 2002 | pmid = 12234665 | doi = 10.1016/S0378-1119(02)00793-X }}

Function

In 2006, DC-SCRIPT was isolated and characterized in human monocyte-derived dendritic cells (mo-DCs).{{cite journal | vauthors = Triantis V, Trancikova DE, Looman MW, Hartgers FC, Janssen RA, Adema GJ | title = Identification and characterization of DC-SCRIPT, a novel dendritic cell-expressed member of the zinc finger family of transcriptional regulators | journal = Journal of Immunology | volume = 176 | issue = 2 | pages = 1081–9 | date = January 2006 | pmid = 16393996 | doi = 10.4049/jimmunol.176.2.1081 | doi-access = free }}

DC-SCRIPT contains a DNA-binding domain (11 C2H2 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 immune system of both mice and humans, DC-SCRIPT was found to be specifically expressed in dendritic cells (DCs).{{cite journal | vauthors = Triantis V, Moulin V, Looman MW, Hartgers FC, Janssen RA, Adema GJ | title = Molecular characterization of the murine homologue of the DC-derived protein DC-SCRIPT | journal = Journal of Leukocyte Biology | volume = 79 | issue = 5 | pages = 1083–91 | date = May 2006 | pmid = 16522745 | doi = 10.1189/jlb.1005588 | hdl-access = free | s2cid = 27847791 | hdl = 2066/49437 }}

In COS-1 cells, DC-SCRIPT was shown to interact with the estrogen receptor DNA-binding domain (ERDBD) and represses ER activity through the association with RIP140, CtBP and histone deacetylases.{{cite journal | vauthors = Lopez-Garcia J, Periyasamy M, Thomas RS, Christian M, Leao M, Jat P, Kindle KB, Heery DM, Parker MG, Buluwela L, Kamalati T, Ali S | display-authors = 6 | title = ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases | journal = Nucleic Acids Research | volume = 34 | issue = 21 | pages = 6126–36 | year = 2006 | pmid = 17085477 | pmc = 1693901 | doi = 10.1093/nar/gkl875 }}

In DCs, DC-SCRIPT was found to be highly expressed in type one conventional DCs (cDC1s) under the control of PU.1.{{cite journal | vauthors = Chopin M, Lun AT, Zhan Y, Schreuder J, Coughlan H, D'Amico A, Mielke LA, Almeida FF, Kueh AJ, Dickins RA, Belz GT, Naik SH, Lew AM, Bouillet P, Herold MJ, Smyth GK, Corcoran LM, Nutt SL | display-authors = 6 | title = Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT | journal = Immunity | volume = 50 | issue = 1 | pages = 77–90.e5 | date = January 2019 | pmid = 30611612 | doi = 10.1016/j.immuni.2018.11.010 | doi-access = free }} 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.{{cite journal | vauthors = Zhang S, Coughlan HD, Ashayeripanah M, Seizova S, Kueh AJ, Brown DV, Cao W, Jacquelot N, D'Amico A, Lew AM, Zhan Y, Tonkin CJ, Villadangos JA, Smyth GK, Chopin M, Nutt SL | display-authors = 6 | title = Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT | journal = Science Immunology | volume = 6 | issue = 58 | pages = eabf4432 | date = April 2021 | pmid = 33811060 | doi = 10.1126/sciimmunol.abf4432 | s2cid = 232771588 }}

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 patients with estrogen receptor- and/or progesterone receptor-positive tumors.{{cite journal | vauthors = Ansems M, Hontelez S, Looman MW, Karthaus N, Bult P, Bonenkamp JJ, Jansen JH, Sweep FC, Span PN, Adema GJ | display-authors = 6 | title = DC-SCRIPT: nuclear receptor modulation and prognostic significance in primary breast cancer | journal = Journal of the National Cancer Institute | volume = 102 | issue = 1 | pages = 54–68 | date = January 2010 | pmid = 20008677 | doi = 10.1093/jnci/djp441 | doi-access = free }}

References

{{reflist}}

Further reading

{{refbegin | 2}}

  • {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
  • {{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | display-authors = 6 | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}
  • {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | display-authors = 6 | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–44 | date = October 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
  • {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | display-authors = 6 | title = The LIFEdb database in 2006 | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D415-8 | date = January 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}

{{refend}}