CYCLIC-AMP SIGNALING PATHWAY AND CELLULAR PROLIFERATION - INDUCTION OF CREM DURING LIVER-REGENERATION

The CREM gene encodes both activators and repressors of cAMP-induced g ene expression, An isoform of CREM encodes the powerful transcriptiona l repressor ICER (Inducible cAMP Early Repressor), which has been show n to be inducible by virtue of an alternative, intronic promoter, The CREM gene belongs to the early response class and displays a character istic neuroendocrine cell- and tissue-specific expression, To date ICE R inducibility has in non-replicating, terminally differentiated In th is paper we document a robust induction of CREM expression in the rege nerating rat liver after partial hepatectomy. This represents the firs t link of inducible CREM expression to the phenomenon of cellular prol iferation, Furthermore, it represents the first example of transcripti onal activation of a cAMP-responsive factor in the regenerating liver, This has significant physiological relevance since the adenylate cycl ase signalling pathway is strongly implicated in liver regeneration, F inally, we show that the repressor ICER is inducible in the hepatoma c ell line H35 upon activation of the adenylate cyclase and phosphorylat ion of the activator CREB.