| First Author | Shinzawa M | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 10758 | PubMed ID | 26029823 |
| Mgi Jnum | J:319680 | Mgi Id | MGI:6216148 |
| Doi | 10.1038/srep10758 | Citation | Shinzawa M, et al. (2015) Catalytic subunits of the phosphatase calcineurin interact with NF-kappaB-inducing kinase (NIK) and attenuate NIK-dependent gene expression. Sci Rep 5:10758 |
| abstractText | Nuclear factor (NF)-kappaB-inducing kinase (NIK) is a serine/threonine kinase that activates NF-kappaB pathways, thereby regulating a wide variety of immune systems. Aberrant NIK activation causes tumor malignancy, suggesting a requirement for precise regulation of NIK activity. To explore novel interacting proteins of NIK, we performed in vitro virus screening and identified the catalytic subunit Aalpha isoform of serine/threonine phosphatase calcineurin (CnAalpha) as a novel NIK-interacting protein. The interaction of NIK with CnAalpha in living cells was confirmed by co-immunoprecipitation. Calcineurin catalytic subunit Abeta isoform (CnAbeta) also bound to NIK. Experiments using domain deletion mutants suggested that CnAalpha and CnAbeta interact with both the kinase domain and C-terminal region of NIK. Moreover, the phosphatase domain of CnAalpha is responsible for the interaction with NIK. Intriguingly, we found that TRAF3, a critical regulator of NIK activity, also binds to CnAalpha and CnAbeta. Depletion of CnAalpha and CnAbeta significantly enhanced lymphotoxin-beta receptor (LtbetaR)-mediated expression of the NIK-dependent gene Spi-B and activation of RelA and RelB, suggesting that CnAalpha and CnAbeta attenuate NF-kappaB activation mediated by LtbetaR-NIK signaling. Overall, these findings suggest a possible role of CnAalpha and CnAbeta in modifying NIK functions. |
