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 accessAbstract
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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Self-citationMice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
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Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice
Bouillon, R., Carmeliet, G., Verlinden, L., van Etten, E., Verstuyf, A., Luderer, H. F., Lieben, L., Mathieu, C., & Demay, M. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0004 · Cited by 1,783
Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression
Wang, T.-T., Nestel, F. P., Bourdeau, V., Nagai, Y., Wang, Q., Liao, J., Tavera-Mendoza, L., Lin, R., Hanrahan, J. W., Mader, S., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.5.2909 · Cited by 1,637
The role of vitamin D in reducing cancer risk and progression
Feldman, D., Krishnan, A. V., Swami, S., Giovannucci, E., & Feldman, B. J. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3691 · Cited by 1,311
Enhanced Growth of Mice Lacking the Cyclin-Dependent Kinase Inhibitor Function of p27
Kiyokawa, H., Kineman, R. D., Manova-Todorova, K. O., Soares, V. C., Hoffman, E. S., Ono, M., Khanam, D., Hayday, A. C., Frohman, L. A., & Koff, A. (1996) · Cell · doi:10.1016/s0092-8674(00)81238-6 · Cited by 1,251
Noncalcemic Actions of Vitamin D Receptor Ligands
Nagpal, S., Na, S., & Rathnachalam, R. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0002 · Cited by 961
Metadata
- Authors
- Liu, M., Lee, M. H., Cohen, M., Bommakanti, M., & Freedman, L. P.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- 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
- diamond
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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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