Zinc finger protein 366, also known asDC-SCRIPT (Dendritic cell-specific transcript), is aprotein that in humans is encoded by theZNF366gene.[5] The ZNF366 gene was first identified in a DNA comparison study between 85 kb ofFugu rubripes sequence containing 17 genes with its homologous loci in the human draftgenome.[6]
DC-SCRIPT contains a DNA-binding domain (11 C2H2zinc (Zn) fingers), flanked by a proline-rich and an acidic region, which can interact with C-terminal-binding protein 1 (CtBP1), a globalcorepressor. In the immune system of bothmice andhumans, DC-SCRIPT was found to be specifically expressed in dendritic cells (DCs).[8]
In COS-1 cells, DC-SCRIPT was shown to interact with theestrogen 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 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.[11]
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 ofbreast cancer patients with estrogen receptor- and/or progesterone receptor-positive tumors.[12]
^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.PMID12234665.
^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.PMID16522745.S2CID27847791.
^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.PMID33811060.S2CID232771588.
