Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection
Date
2009
Authors
Johnson, Andy L
Aravind, L
Schulzhenko, Natalia
Morgun, Andre
Choi, See-Young
Crockford, Tanya
Lambe, Teresa
Domaschenz, Heather
Kucharska, Edyta
Zhang, Lixin
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Nature Publishing Group
Abstract
T cell antigen receptor (TCR) signaling in CD4+CD8+ double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.
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Keywords: cell protein; cysteine; ethylnitrosourea; growth factor receptor bound protein 2; T lymphocyte receptor; thymus expressed molecule involved in selection protein; unclassified drug; animal cell; article; CD4 CD8 ratio; cell cycle; cell lineage; cell select
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Nature Immunology
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Journal article
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2037-12-31
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