ZNF366

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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UniProt
RefSeq (mRNA)

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RefSeq (protein)

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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.[1] 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.[2]

Function

In 2006, DC-SCRIPT was isolated and characterized in human monocyte-derived dendritic cells (mo-DCs).[3]

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).[4]

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.[5]

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.[6]

References

  1. "Entrez Gene: ZNF366 zinc finger protein 366".
  2. 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.
  3. 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". J. Immunol. 176 (2): 1081–9. doi:10.4049/jimmunol.176.2.1081. PMID 16393996.
  4. 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". J. Leukoc. Biol. 79 (5): 1083–91. doi:10.1189/jlb.1005588. PMID 16522745.
  5. 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 (2006). "ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases". Nucleic Acids Res. 34 (21): 6126–36. doi:10.1093/nar/gkl875. PMC 1693901. PMID 17085477.
  6. Ansems M, Hontelez S, Looman MW, Karthaus N, Bult P, Bonenkamp JJ, Jansen JH, Sweep FC, Span PN, Adema GJ (January 2010). "DC-SCRIPT: nuclear receptor modulation and prognostic significance in primary breast cancer". J. Natl. Cancer Inst. 102 (1): 54–68. doi:10.1093/jnci/djp441. PMID 20008677.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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