Document Detail

Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells.
MedLine Citation:
PMID:  8542578     Owner:  NLM     Status:  MEDLINE    
Progression of mammalian cells through G1 is controlled by the concerted action of protein kinases, the activities of which are modulated in both positive (cyclins) and negative [cyclin-dependent kinase inhibitors (CDIs)] manners by families of regulatory proteins. In differentiation of leukemia cells, a G1 arrest is a common, if not invariable, occurence and takes place after the appearance of markers of monocytic differentiation in human leukemia HL60 cells treated with 1,25 dihydroxyvitamin D3 (1,25D3) at low to moderately high concentrations (F. Zhang et al., Cell Proliferation 27: 643-654, 1994). In the present study, we investigated the protein levels of several G1 regulatory proteins that are potential mediators of the 1,25D3-induced G1 block. During the first 24 h of exposure to a high concentration (4 x 10(-7) M) of 1,25D3, no increase was noted in the immunodetectable levels of cyclins D1 or E, or CDIs p16Ink4, p21Cip1/Waf1, or p27Kip1, even though monocytic differentiation markers were evident, and a prolongation of G1 was noted. After 48 h of exposure 4 x 10(-7) M to 1,25D3, a G1 to S-phase block progressively increased in parallel with the abundance of the p27Kip1 CDI. A transient increase in p21Cip1/Waf1 was noted only at 48 hr. The increase in p27Kip1 protein level was dependent on the concentration of 1,25D3 and was accompanied by an increase in cyclin D and E proteins, which normally peak in mid-G1 and at the G1 to S-phase transition, respectively. These results indicate that p27Kip1 protein is a strong candidate for the cell cycle regulator that blocks the entry into the S-phase in 1,25D3-treated HL60 cells.
Q M Wang; J B Jones; G P Studzinski
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  56     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1996 Jan 
Date Detail:
Created Date:  1996-02-13     Completed Date:  1996-02-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  264-7     Citation Subset:  IM    
Department of Laboratory Medicine and Pathology, UMD-New Jersey Medical School, Newark 07103, USA.
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MeSH Terms
Calcitriol / pharmacology*
Cell Cycle Proteins*
Cell Differentiation / drug effects
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases / antagonists & inhibitors
Enzyme Inhibitors / metabolism
G1 Phase / drug effects*
HL-60 Cells / cytology*,  drug effects*,  metabolism
Microtubule-Associated Proteins / metabolism*
Monocytes / cytology,  drug effects
S Phase / drug effects*
Tumor Suppressor Proteins*
Up-Regulation / drug effects
Grant Support
Reg. No./Substance:
0/Cdkn1b protein, mouse; 0/Cdkn1b protein, rat; 0/Cell Cycle Proteins; 0/Enzyme Inhibitors; 0/Microtubule-Associated Proteins; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 32222-06-3/Calcitriol; EC Kinases

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