ZNF366

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.[5] 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.[6]

ZNF366
Identifiers
AliasesZNF366, DCSCRIPT, zinc finger protein 366, DC-SCRIPT
External IDsOMIM: 610159 MGI: 2178429 HomoloGene: 17637 GeneCards: ZNF366
Orthologs
SpeciesHumanMouse
Entrez

167465

238803

Ensembl

ENSG00000178175

ENSMUSG00000050919

UniProt

Q8N895

Q6NS86

RefSeq (mRNA)

NM_152625

NM_001004149

RefSeq (protein)

NP_689838

NP_001004149

Location (UCSC)Chr 5: 72.44 – 72.51 MbChr 13: 99.32 – 99.39 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

In 2006, DC-SCRIPT was isolated and characterized in human monocyte-derived dendritic cells (mo-DCs).[7]

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).[8]

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.[9]

In DCs, DC-SCRIPT was found to be highly expressed in type one conventional DCs (cDC1s) under the control of PU.1.[10] The presence of DC-SCRIPT is important for the cDC1s linage 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.[11]

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.[12]

References
  1. GRCh38: Ensembl release 89: ENSG00000178175 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000050919 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: ZNF366 zinc finger protein 366".
  6. Gilligan P, Brenner S, Venkatesh B (July 2002). "Fugu and human sequence comparison identifies novel human genes and conserved non-coding sequences". Gene. 294 (1–2): 35–44. doi:10.1016/S0378-1119(02)00793-X. PMID 12234665.
  7. Triantis V, Trancikova DE, Looman MW, Hartgers FC, Janssen RA, Adema GJ (January 2006). "Identification and characterization of DC-SCRIPT, a novel dendritic cell-expressed member of the zinc finger family of transcriptional regulators". Journal of Immunology. 176 (2): 1081–9. doi:10.4049/jimmunol.176.2.1081. PMID 16393996.
  8. Triantis V, Moulin V, Looman MW, Hartgers FC, Janssen RA, Adema GJ (May 2006). "Molecular characterization of the murine homologue of the DC-derived protein DC-SCRIPT". Journal of Leukocyte Biology. 79 (5): 1083–91. doi:10.1189/jlb.1005588. hdl:2066/49437. PMID 16522745. S2CID 27847791.
  9. Lopez-Garcia J, Periyasamy M, Thomas RS, Christian M, Leao M, Jat P, et al. (2006). "ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases". Nucleic Acids Research. 34 (21): 6126–36. doi:10.1093/nar/gkl875. PMC 1693901. PMID 17085477.
  10. Chopin M, Lun AT, Zhan Y, Schreuder J, Coughlan H, D'Amico A, et al. (January 2019). "Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT". Immunity. 50 (1): 77–90.e5. doi:10.1016/j.immuni.2018.11.010. PMID 30611612.
  11. Zhang S, Coughlan HD, Ashayeripanah M, Seizova S, Kueh AJ, Brown DV, et al. (April 2021). "Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT". Science Immunology. 6 (58): eabf4432. doi:10.1126/sciimmunol.abf4432. PMID 33811060. S2CID 232771588.
  12. Ansems M, Hontelez S, Looman MW, Karthaus N, Bult P, Bonenkamp JJ, et al. (January 2010). "DC-SCRIPT: nuclear receptor modulation and prognostic significance in primary breast cancer". Journal of the National Cancer Institute. 102 (1): 54–68. doi:10.1093/jnci/djp441. PMID 20008677.

Further reading

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