| First Author | Esau C | Year | 2001 |
| Journal | J Exp Med | Volume | 194 |
| Issue | 10 | Pages | 1449-59 |
| PubMed ID | 11714752 | Mgi Jnum | J:72760 |
| Mgi Id | MGI:2153565 | Doi | 10.1084/jem.194.10.1449 |
| Citation | Esau C, et al. (2001) Deletion of Calcineurin and Myocyte Enhancer Factor 2 (MEF2) Binding Domain of Cabin1 Results in Enhanced Cytokine Gene Expression in T Cells. J Exp Med 194(10):1449-59 |
| abstractText | Cabin1 binds calcineurin and myocyte enhancer factor 2 (MEF2) through its COOH-terminal region. In cell lines, these interactions were shown to inhibit calcineurin activity after T cell receptor (TCR) signaling and transcriptional activation of Nur77 by MEF2. The role of these interactions under physiological conditions was investigated using a mutant mouse strain that expresses a truncated Cabin1 lacking the COOH-terminal calcineurin and MEF2 binding domains. T and B cell development and thymocyte apoptosis were normal in mutant mice. In response to anti-CD3 stimulation, however, mutant T cells expressed significantly higher levels of interleukin (IL)-2, IL-4, IL-9, IL-13, and interferon gamma than wild-type T cells. The enhanced cytokine gene expression was not associated with change in nuclear factor of activated T cells (NF-AT)c or NF-ATp nuclear translocation but was preceded by the induction of a phosphorylated form of MEF2D in mutant T cells. Consistent with the enhanced cytokine expression, mutant mice had elevated levels of serum immunoglobulin (Ig)G1, IgG2b, and IgE and produced more IgG1 in response to a T cell-dependent antigen. These findings suggest that the calcineurin and MEF2 binding domain of Cabin1 is dispensable for thymocyte development and apoptosis, but is required for proper regulation of T cell cytokine expression probably through modulation of MEF2 activity. |
