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Cited by 890

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

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

Open access
Liu, M, Lee, M H, Cohen, M, Bommakanti, M, Freedman, L P·1996·Genes & Development

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.

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Metadata

Authors
Liu, M., Lee, M. H., Cohen, M., Bommakanti, M., & Freedman, L. P.
Venue
Genes & Development
Published
1996-01-15
Volume
10
Issue
2
Pages
142-153
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2162741492
Cited by
890
References
58
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. https://app.cochat.ai/papers/10.1101/gad.10.2.142
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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. https://doi.org/10.1101/gad.10.2.142

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