title: Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection.
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.
authors: Nuffield Department of Clinical Medicine, Oxford University, UK.
authors: Andy L
authors: AL
authors: Johnson
authors: L
authors: L
authors: Aravind
authors: Natalia
authors: N
authors: Shulzhenko
authors: Andre
authors: A
authors: Morgun
authors: See-Young
authors: SY
authors: Choi
authors: Tanya L
authors: TL
authors: Crockford
authors: Teresa
authors: T
authors: Lambe
authors: Heather
authors: H
authors: Domaschenz
authors: Edyta M
authors: EM
authors: Kucharska
authors: Lixin
authors: L
authors: Zheng
authors: Carola G
authors: CG
authors: Vinuesa
authors: Michael J
authors: MJ
authors: Lenardo
authors: Christopher C
authors: CC
authors: Goodnow
authors: Richard J
authors: RJ
authors: Cornall
authors: Ronald H
authors: RH
authors: Schwartz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D005038:Ethylnitrosourea / Q000494:pharmacology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C544192:themis protein, mouse; D005038:Ethylnitrosourea