Choline Kinase alpha Expression during RA-induced Neuronal Differentiation: role of C/EBPb?

DOMIZI, P AND BANCHIO C

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

ELSEVIER SCIENCE BV

Año: 2014 vol. 1841 p. 544 - 555

1388-1981

Neuronal differentiation is a complex process characterized by a halt inproliferation and extension of neurites from the cell body. This process isaccompanied by changes in gene expression that mediate the redirectionleading to neurite formation and function. Acceleration of membranephospholipids synthesis is associated with neurite elongation, andphosphatidylcholine (PtdCho) is the major membrane phospholipid inmammalian cells. The transcription of two genes in particular encoding keyenzymes in the CDP-choline pathway for PtdCho biosynthesis are stimulated;the Chka gene for choline kinase (CK) alpha isoform and the Pcyt1a gene forthe CTP:phosphocholine cytidylyltransferase (CCT) alpha isoform. We reportthat the stimulation of CK expression during retinoic acid (RA) induceddifferentiation depend on a promoter region that contains twoCCAAAT/Enhancer-binding Protein- (C/EBP sites). We demonstrate thatduring neuronal differentiation of Neuro-2a cells, RA induces Chka expressionby a mechanism that involves ERK1/2 activation which triggers C/EBPexpression. Elevated levels of C/EBP bind to the Chka proximal promoter(Box1) inducing CK expression. In addition we identified a downstreamsequence named Box2 which together with Box1 is required for the promoter toreach the full induction. This is the first elucidation of the mechanism by whichthe expression of Chka is coordinately regulated during neuronal differentiation.