Calcyclin-binding protein/Siah-1-interacting protein as a regulator of transcriptional responses in brain cells.

The calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) is highly expressed in the brain and has been shown to regulate β-catenin-driven transcription in thymocytes. Therefore, we investigated whether CacyBP/SIP plays a role as a transcriptional regulator in brain cells. In brain-derived neurotrophic factor (BDNF)- and forskolin-stimulated rat primary cortical neurons, overexpression of CacyBP/SIP enhanced transcriptional activity of the cAMP-response element (CRE). In addition, overexpressed CacyBP/SIP enhanced BDNF-mediated activation of the nuclear factor of activated T cells (NFAT) but not the serum response element (SRE). These stimulatory effects required an intact C-terminal domain of CacyBP/SIP. Moreover, in C6 rat glioma cells, the overexpressed CacyBP/SIP enhanced activation of CRE and NFAT following forskolin and serum stimulation, respectively. Conversely, knockdown of endogenous CacyBP/SIP reduced activation of CRE and NFAT but not of SRE. Taken together, these results indicate that CacyBP/SIP is a novel regulator of CRE- and NFAT-driven transcription.