Involvement of nucleophosmin/B23 in TPA-induced megakaryocytic differentiation of K562 cells.
Human myelogenous leukaemia K562 cells were induced to undergo megakaryocytic differentiation by treatment with phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (20 nM, 24-72 h). The steady-state level of nucleophosmin/B23 mRNA decreased during the TPA-induced differentiation. There was also decrease in the level of cellular nucleophosmin/B23 protein and appearance of its degraded product (25 kDa) during the TPA-induced differentiation. Furthermore, K562/B23 (wild type), K562/D1 (delta280-294) and K562/D2 (delta263-294) cells were less, while K562/D3 (delta244-294) cells were more responsive to TPA-induced differentiation as compared to K562/vector or parental K562 cells. Activation of the ERK/MAPK was observed in parental K562 cells upon TPA treatment (5 nM, 5-30 min). As compared to K562/vector cells, less activation of ERK/MAPK was observed in K562/D2 cells, while ERK/MAPK was highly activated in K562/D3 cells upon TPA treatment. Our results indicate that nucleophosmin/B23 plays an important role in TPA-induced differentiation of K562 cells and the amino acids 244-294 at C-terminal of nucleophosmin/B23 could be an important site for regulation of cellular response to differentiation.
Hsu
C Y
CY
Graduate Institute of Pharmacology, National Yang Ming University, Taiwan, Republic of China.
Yung
B Y M
BY
D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells / Q000473:pathology; D008533:Megakaryocytes / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D009697:Nucleolus Organizer Region; D000090243:Nucleophosmin; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D002273:Carcinogens; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate