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 towards the macrophage lineage. PMA-induced 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 pathway is essential to PMA-induced differentiation of HL60 cells. PMA also induces the expression of the cyclin-dependent kinase inhibitors p21(WAF) and p27(kip1), which is modulated by the use of an inhibitor of the ERK cascade. This implies that a link exists between ERK activation and p21(WAF) and p27(kip1) induction in the process of terminal differentiation.
Das
D
D
Department of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Pintucci
G
G
Stern
A
A
D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002457:Cell Extracts; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D002457:Cell Extracts; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate