title: Calcyclin-binding protein/Siah-1-interacting protein as a regulator of transcriptional responses in brain cells.
abstract: 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.
authors.affiliation: Kentucky Spinal Cord Injury Research Center and Department of Neurological Surgery, University of Louisville, Louisville, Kentucky; Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kilanczyk
authors.forename: Anna
authors.initials: A
authors.lastname: Filipek
authors.forename: Michal
authors.initials: M
authors.lastname: Hetman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D050778:NFATC Transcription Factors / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005576:Colforsin; D050882:CREB-Binding Protein; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
keywords: CRE-driven transcription; CacyBP/SIP; brain development