MAPK-dependent expression of p21(WAF) and p27(kip1) in PMA-induced differentiation of HL60 cells

Treatment of HL60 cells with phorbol 12-myristate 13-acetate (PMA) results in growth arrest and differentiation ton ards the macrophage lineage. PMA-i nduced changes are easily monitored by morphological changes while cells in suspension start adhering onto substrate, PMA induces rapid activation of the extracellular signal-regulated kinases (ERKs), Activation of the ERK pa thway is essential to PMA-induced differentiation of HL60 cells. PMA also i nduces the expression of the cyclin-dependent kinase inhibitors p21(WAF) an d p27(kip1) which is modulated by the use of an inhibitor of the ER cascade . This implies that a Link exists between ERK activation and p21(WAF) and p 27(kip1) induction in the process of terminal differentiation. (C) 2000 Fed eration of European Biochemical Societies.