Direct protein-protein interaction between Npas4 and IPAS mutually inhibits their critical roles in neuronal cell survival and death.

ABSTRACT: Inhibitory PAS domain protein (IPAS) is a bifunctional protein that acts as a transcriptional repressor in hypoxia and as a pro-apoptotic protein involved in neuronal cell death. Npas4 (NXF or LE-PAS) is a transcriptional factor that protects nerve cells from endogenous and foreign neurotoxins. Here we show that IPAS and Npas4 antagonize each other through their direct interaction. Coimmunoprecipitation experiments revealed that multiple binding sites on each protein were involved in the interaction. CoCl₂ treatment of PC12 cells that induces IPAS repressed the transactivation activity of Npas4, and IPAS siRNA treatment reduced the CoCl₂-induced repression. CoCl₂-induced apoptosis was suppressed by the addition of KCl that induces Npas4. The protective effe

SUBMITTER: Kasai S 

PROVIDER: S-EPMC8531447 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature