Themis is a member of a new metazoan gene family and is required for completion of thymocyte positive selection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-07-13

AUTHORS

Andy L. Johnson, L. Aravind, Natalia Shulzhenko, Andriy Morgun, See-Young Choi, Tanya L. Crockford, Teresa Lambe, Heather Domaschenz, Edyta Kucharska, Lixin Zheng, Carola C. Vinuesa, Michael J. Lenardo, Christopher C. Goodnow, Richard J. Cornall, Ronald H. Schwartz

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. More... »

PAGES

831-839

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni.1769

DOI

http://dx.doi.org/10.1038/ni.1769

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009622882

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19597497


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35 schema:description 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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43 THEMIS
44 Themis-deficient thymocytes
45 altered expression
46 animal species
47 antigen receptor
48 basis
49 cell antigen receptor
50 cell cycle
51 cell survival
52 commitment
53 completion
54 cycle
55 cysteine motif
56 data
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58 domain
59 double-positive thymocytes determines cell survival
60 early TCR signaling
61 ethylnitrosourea mutagenesis
62 expression
63 family
64 function
65 gene family
66 genes
67 globular domain
68 impairment
69 issues
70 lineage commitment
71 lineage-specific genes
72 members
73 metazoan gene families
74 molecular basis
75 most animal species
76 motif
77 mutagenesis
78 new metazoan gene family
79 orthologs
80 positive selection
81 process
82 protein
83 receptors
84 repeats
85 selection
86 signaling
87 species
88 substantial impairment
89 survival
90 tandem repeats
91 thymocyte positive selection
92 thymocytes
93 thymocytes determines cell survival
94 uncharacterized vertebrate proteins
95 unique function
96 unique globular domain
97 vertebrate proteins
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