Document Detail

Activin A-induced differentiation in K562 cells is associated with a transient hypophosphorylation of RB protein and the concomitant block of cell cycle at G1 phase.
MedLine Citation:
PMID:  1361489     Owner:  NLM     Status:  MEDLINE    
The human erythroleukemic cell line, K562, can be induced to differentiate by the addition of activin A, a newly purified protein belonging to the TGF-beta 1 family. The present studies used flow cytometric cell cycle analysis, indirect immunofluorescence staining of the proliferating cell nuclear antigen (PCNA), and thymidine incorporation assay of cell proliferation to study the effects of activin A on the cell cycle during differentiation in K562 cells. Activin A-treated K562 cells were found to undergo a transient block in cell cycle, temporarily halting progression from G1 to S phase. The latter can be observed after approximately 24 hr of incubation with activin A and then disappears after this early stage of induction of differentiation. Cell cycle kinetics analysis using synchronized K562 cells also confirms that in the presence of activin A, K562 cells progress normally through various phases of cell cycle, except that there is prolongation of the G1 phase between 10 to 24 hr of culture. Furthermore, this transient arrest in G1 is correlated with dephosphorylation of a nucleoprotein, the RB gene product, which occurs within 9-24 hr of incubation with activin A; and phosphorylation of RB protein then develops afterward. In addition, these cell cycle-related events are observed to occur earlier than the accumulation of hemoglobins in K562 cells. It is concluded that transient dephosphorylation of RB protein and prolongation of G1 phase of cell cycle precede and accompany erythroid differentiation caused by activin A and chemical inducers, thus constituting part of the mechanism for induction of differentiation in the erythroleukemia cells.
D W Sehy; L E Shao; A L Yu; W M Tsai; J Yu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  50     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1993-01-28     Completed Date:  1993-01-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  255-65     Citation Subset:  IM    
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
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MeSH Terms
Cell Cycle / drug effects*
Cell Differentiation / drug effects*
Inhibins / pharmacology*
Leukemia, Erythroblastic, Acute
Nuclear Proteins / metabolism
Proliferating Cell Nuclear Antigen
Retinoblastoma Protein / metabolism*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Nuclear Proteins; 0/Proliferating Cell Nuclear Antigen; 0/Retinoblastoma Protein; 104625-48-1/Activins; 57285-09-3/Inhibins

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