The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes
Open accessAbstract
The tumor suppressor p53 functions predominantly as a transcription factor by activating and downregulating gene expression, leading to cell cycle arrest or apoptosis. p53 was shown to indirectly repress transcription of the CCNB2, KIF23 and PLK4 cell cycle genes through the recently discovered p53-p21-DREAM-CDE/CHR pathway. However, it remained unclear whether this pathway is commonly used. Here, we identify genes regulated by p53 through this pathway in a genome-wide computational approach. The bioinformatic analysis is based on genome-wide DREAM complex binding data, p53-depedent mRNA expression data and a genome-wide definition of phylogenetically conserved CHR promoter elements. We find 210 target genes that are expected to be regulated by the p53-p21-DREAM-CDE/CHR pathway. The target gene list was verified by detailed analysis of p53-dependent repression of the cell cycle genes B-MYB (MYBL2), BUB1, CCNA2, CCNB1, CHEK2, MELK, POLD1, RAD18 and RAD54L. Most of the 210 target genes are essential regulators of G2 phase and mitosis. Thus, downregulation of these genes through the p53-p21-DREAM-CDE/CHR pathway appears to be a principal mechanism for G2/M cell cycle arrest by p53.
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“DREAM (dimerization partner, RB‐like, E2F, and multi‐vulval class B) is a multi‐protein complex localized in the CHR box of the promoters of hundreds of cell‐cycle‐regulated genes associated with the regulation of cellular checkpoints, DNA replication, or DNA repair [75].”
From The TP53 tumor suppressor gene: From molecular biology to clinical investigations (2025) · cites this paper as [75]
In the citing paper
“p53 represses CDKs and cyclin B, which are required for entry into mitosis and are involved in G2/M phase block.62,63”
From Targeting p53 pathways: mechanisms, structures, and advances in therapy (2023) · cites this paper as [62]
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 3,971 · cited 1×
“PhastCons conservation scores (35) obtained from the multiz46 alignment of placental mammalia (36) were used to calculate average phylogenetic sequence conservation.”
MethodBlinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967
Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner
Blanchette, M., Kent, W. J., Riemer, C., Elnitski, L., Smit, A. F. A., Roskin, K. M., Baertsch, R., Rosenbloom, K., Clawson, H., Green, E. D., et al. (2004) · Genome Research · doi:10.1101/gr.1933104 · Cited by 1,452
A Global Map of p53 Transcription-Factor Binding Sites in the Human Genome
Wei, C.-L., Wu, Q., Vega, V. B., Chiu, K. P., Ng, P., Zhang, T., Shahab, A., Yong, H. C., Fu, Y., Weng, Z., et al. (2006) · Cell · doi:10.1016/j.cell.2005.10.043 · Cited by 1,141
The DREAM complex: master coordinator of cell cycle-dependent gene expression
Sadasivam, S., & DeCaprio, J. A. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3556 · Cited by 524
Chang, B.-D., Watanabe, K., Broude, E. V., Fang, J., Poole, J. C., Kalinichenko, T. V., & Roninson, I. B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4291 · Cited by 432
Litovchick, L., Sadasivam, S., Florens, L., Zhu, X., Swanson, S. K., Velmurugan, S., Chen, R., Washburn, M. P., Liu, X. S., & DeCaprio, J. A. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.04.015 · Cited by 396
Cited by
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622
The multiple mechanisms that regulate p53 activity and cell fate
Hafner, A., Bulyk, M. L., Jambhekar, A., & Lahav, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0110-x · Cited by 1,129
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971
Self-citationTargeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016
p21: a two-faced genome guardian.
Georgakilas, A. G., Martin, O. A., & Bonner, W. M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.02.001 · Cited by 489
Metadata
- Authors
- Fischer, M., Quaas, M., Steiner, L., & Engeland, K.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-17
- Volume
- 44
- Issue
- 1
- Pages
- 164-174
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W1442157793
- Cited by
- 321
- References
- 67
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- gold
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- Fischer, M., Quaas, M., Steiner, L., & Engeland, K. (2016). The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes. Nucleic Acids Research. https://doi.org/10.1093/nar/gkv927
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