| First Author | Lucena PI | Year | 2016 |
| Journal | Mol Cell Biol | Volume | 36 |
| Issue | 1 | Pages | 119-31 |
| PubMed ID | 26483414 | Mgi Jnum | J:235918 |
| Mgi Id | MGI:5803943 | Doi | 10.1128/MCB.00501-15 |
| Citation | Lucena PI, et al. (2016) NFAT2 Isoforms Differentially Regulate Gene Expression, Cell Death, and Transformation through Alternative N-Terminal Domains. Mol Cell Biol 36(1):119-31 |
| abstractText | The NFAT (nuclear factor of activated T cells) family of transcription factors is composed of four calcium-responsive proteins (NFAT1 to -4). The NFAT2 (also called NFATc1) gene encodes the isoforms NFAT2alpha and NFAT2beta that result mainly from alternative initiation exons that provide two different N-terminal transactivation domains. However, the specific roles of the NFAT2 isoforms in cell physiology remain unclear. Because previous studies have shown oncogenic potential for NFAT2, this study emphasized the role of the NFAT2 isoforms in cell transformation. Here, we show that a constitutively active form of NFAT2alpha (CA-NFAT2alpha) and CA-NFAT2beta distinctly control death and transformation in NIH 3T3 cells. While CA-NFAT2alpha strongly induces cell transformation, CA-NFAT2beta leads to reduced cell proliferation and intense cell death through the upregulation of tumor necrosis factor alpha (TNF-alpha). CA-NFAT2beta also increases cell death and upregulates Fas ligand (FasL) and TNF-alpha in CD4(+) T cells. Furthermore, we demonstrate that differential roles of NFAT2 isoforms in NIH 3T3 cells depend on the N-terminal domain, where the NFAT2beta-specific N-terminal acidic motif is necessary to induce cell death. Interestingly, the NFAT2alpha isoform is upregulated in Burkitt lymphomas, suggesting an isoform-specific involvement of NFAT2 in cancer development. Finally, our data suggest that alternative N-terminal domains of NFAT2 could provide differential mechanisms for the control of cellular functions. |
