title: Distinct effect of CacyBP/SIP on the ERK1/2-CREB-BDNF pathway in undifferentiated and differentiated neuroblastoma NB2a cells.
abstract: CacyBP/SIP, a protein expressed to high extent in the brain, has been shown to act as ERK1/2 phosphatase in vitro and in cultured cells. It has been demonstrated recently that CacyBP/SIP can modulate the activity of some transcription factors in neurons and glioma cells. In the present work we have examined the effect of CacyBP/SIP overexpression and silencing on the phosphorylation/activity of ERK1/2 (pERK1/2) and CREB (pCREB) and on the level of BDNF mRNA in differentiated and undifferentiated neuroblastoma NB2a cells. We have shown that in undifferentiated cells the amount of pERK1/2 decreased upon CacyBP/SIP overexpression. Further studies have shown that the activity of CREB and the level of BDNF mRNA, downstream effectors of the ERK1/2 signaling pathway, also depended on the CacyBP/SIP level and strictly matched the level of pERK1/2. Interestingly, in differentiated NB2a cells, overexpression of CacyBP/SIP appeared to have a distinct effect on the pERK1/2 level from that observed in undifferentiated cells. Subsequent studies have revealed that distinct function of CacyBP/SIP in undifferentiated and differentiated NB2a cells might be due to changes in its posttranslational modifications and protein ligands. Altogether, our studies suggest that CacyBP/SIP is involved in the ERK1/2-CREB-BDNF pathway and that it might regulate this pathway depending on the stage of NB2a cell differentiation.
authors.affiliation: Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland.
authors.forename: Sara
authors.initials: S
authors.lastname: Rosińska
authors.affiliation: Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland.
authors.forename: Wiesława
authors.initials: W
authors.lastname: Leśniak
authors.affiliation: Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland. Electronic address: a.filipek@nencki.gov.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Filipek
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C111922:Cacybp protein, mouse; D002135:Calcium-Binding Proteins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein
keywords: BDNF; CREB; CacyBP/SIP; Cell differentiation; ERK1/2; NB2a cells