Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway.
The retinoblastoma tumor suppressor (Rb) gene product plays an essential role in cell-cycle regulation. However, its role in terminal differentiation of hematopoietic cells is speculative. Here we show a model of 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced hematopoietic differentiation and growth arrest with a defective Rb-mediated pathway. TPA treatment arrested the cell cycle of a human hematopoietic cell line, MEG-01s, at the G1-S boundary and induced expression of p21/SDI1/WAF1/CIP1 and p27/KIP1. Both of these proteins were present in cyclin E-associated complexes, the histone H1 and Rb kinase activities of which were then inactivated. However, MEG-01s cells lacked the intact Rb protein and the Rb-mediated pathway was defective. This model raises a question about the role for Rb in terminal differentiation of hematopoietic cells.
Uchimaru
K
K
Fourth Department of Internal Medicine, University of Tokyo, School of Medicine, Japan.
Taniguchi
T
T
Yoshikawa
M
M
Fujinuma
H
H
Fujita
T
T
Motokura
T
T
D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019927:Cyclin E / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D016213:Cyclins / Q000032:analysis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000032:analysis; D005434:Flow Cytometry; D015870:Gene Expression; D016161:Genes, Retinoblastoma / Q000235:genetics* / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000503:physiopathology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis; D016196:S Phase; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D013755:Tetradecanoylphorbol Acetate