DOI: 10.1101/gad.10.2.142. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937.

Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937.

10.1101/gad.10.2.142

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, acting through its cognate nuclear receptor (vitamin D3 receptor, VDR) will induce myeloid leukemic cell lines to terminally differentiate into monocytes/macrophages. Because VDR acts by transcriptionally regulating responsive genes in a ligand-dependent manner, we sought target genes of the receptor that initiate, the differentiation process in response to ligand. We screened a cDNA library prepared from the myelomonocytic U937 cell line with probes generated from either 1,25-dihydroxyvitamin D3-treated or untreated cells. We report here that a candidate clone that hybridized differentially is the Cdk inhibitor p21WAF1, CIP1. Furthermore, we show that p21 is transcriptionally induced by 1,25-dihydroxyvitamin D3 in a VDR-dependent, but not p53-dependent, manner, and we identify a functional vitamin D response element in the p21 promoter. Transient overexpression of p21 and/or the related Cdk inhibitor p27 in U937 cells in the absence of 1,25-dihydroxyvitamin D3 results in the cell-surface expression of monocyte/macrophage-specific markers, suggesting that ligand-modulated transcriptional induction of the p21 gene facilitates the induced differentiation of this monoblastic cell line. We believe that this is the first report demonstrating that the ectopic overexpression of a Cdk inhibitor such as p21 or p27 directly leads to a terminal differentiation program.

Bibliography

Liu, M., Lee, M. H., Cohen, M., Bommakanti, M., & Freedman, L. P. (1996). Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes & Development, 10(2), 142â153.

Authors 5

M Liu (first)
M H Lee (additional)
M Cohen (additional)
M Bommakanti (additional)
L P Freedman (additional)

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Dates

Type	When
Created	18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited	2 years, 3 months ago (May 12, 2023, 2:24 a.m.)
Indexed	3 weeks, 5 days ago (July 30, 2025, 10:58 a.m.)
Issued	29 years, 7 months ago (Jan. 15, 1996)
Published	29 years, 7 months ago (Jan. 15, 1996)
Published Online	29 years, 7 months ago (Jan. 15, 1996)
Published Print	29 years, 7 months ago (Jan. 15, 1996)

Funders 0

None

BibTeX

@article{Liu_1996, title={Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937.}, volume={10}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.10.2.142}, DOI={10.1101/gad.10.2.142}, number={2}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Liu, M and Lee, M H and Cohen, M and Bommakanti, M and Freedman, L P}, year={1996}, month=jan, pages={142–153} }

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