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Identification and Characterization of DC-SCRIPT, a Novel Dendritic Cell-Expressed Member of the Zinc Finger Family of Transcriptional Regulators¹

Vassilis Triantis^*, Dagmar Eleveld Trancikova^*, Maaike W. G. Looman^*, Franca C. Hartgers, Richard A. J. Janssen and Gosse J. Adema^2,*

^* Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; and Galádeno, Leiden, The Netherlands

Dendritic cells (DC) compose a heterogeneous population of cells that hold a leading role in initiating and directing immune responses. Although their function in recognizing, capturing, and presenting Ags is well defined, the molecular mechanisms that control their differentiation and immune functions are still largely unknown. In this study, we report the isolation and characterization of DC-SCRIPT, a novel protein encoded by an 8-kb mRNA that is preferentially expressed in DC. DC-SCRIPT is expressed in multiple DC subsets in vivo, including myeloid DC, plasmacytoid DC, and Langerhans cells. At the protein level, DC-SCRIPT consists of a proline-rich region, 11 C₂H₂-type zinc fingers, and an acidic region. Localization studies reveal that DC-SCRIPT resides in the nucleus and that nuclear localization is critically dependent on the zinc fingers. The protein displays no transcriptional activation properties according to assorted transactivation assays, but interacts with the corepressor C-terminal binding protein 1. Taken together, our results show that we have isolated a novel DC marker that could be involved in transcriptional repression. In contrast to other DC molecules, DC-SCRIPT identifies all DC subsets tested to date.

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