Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5507759 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | 2017 | 49 Pages |
Abstract
The aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an “EPA-cyclic AMP response element-binding protein (CREB)” signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1]2:ID2:E47 tetrameric complex.In essence, the molecular function of CREB1 is to dynamically regulate the location-specific assembly or disassembly of basic-helix-loop-helix (bHLH):HLH protein complexes to mediate the activation of neural/glial target genes. Together, these findings support the one-to-many binding mechanism of CREB1 and indicate that EPA treatment potentiates the integration of CREB dependent signaling with HLH/bHLH transcriptional network, adding specificity to the CREB1-mediated gene regulation during neural/glial differentiation. Our current research on the EPA-CREB axis could reveal new molecular targets for treating neurogenerative disease.
Keywords
Retinoid X receptorinhibitor of DNA bindingLIFmESCRXRGPR40PLPCREBPUFAsbHLHPPAREPACa2 +Proteolipid proteinBasic-helix-loop-helixEicosapentaenoic acidPolyunsaturated fatty acidsRetinoic acidEmbryonic stem cellMouse embryonic stem cellsLipid signalingleukemia inhibitory factorMultiprotein complexcyclic AMP response element-binding proteinperoxisome proliferator-activated receptor
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Authors
Maurizio Rossi, Martin Spichty, Lucilla Attorri, Chiara Distante, Clara Nervi, Serafina Salvati, Luigi Vitelli,