c-Jun N-terminal kinase controls a negative loop in the regulation of glial fibrillary acidic protein expression by retinoic acid.

Glial fibrillary acidic protein (GFAP) is a protein widely used as a molecular marker for astroglial differentiation and mature astrocytes. We and others have shown previously that retinoic acid and specific cytokines induce the expression of GFAP in neural precursor cells by activating the phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K) phosphorylation pathway. Here, we extend our previous work and show that retinoic acid also activates specifically the c-Jun N-terminal kinase (JNK) phosphorylation pathway, which in turn inhibits GFAP expression. Our results suggest the existence of a negative self-regulatory loop in the phosphorylation pathways that regulates GFAP expression. This loop is constitutively repressed by the PI3K pathway. Our results could be relevant for disorders involving sustained GFAP overexpression in precursor cells, such as glioblastoma and Alexander disease.