ArticleMolecular and cellular biology2008
Myc inhibits p27-induced erythroid differentiation of leukemia cells by repressing erythroid master genes without reversing p27-mediated cell cycle arrest.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells.Cell death & disease · 2018Pooled it
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- ARNT2 repression disrupts neuronal identity and promotes glioblastoma growth.Cell communication and signaling : CCS · 2026Article
- CellFM: a large-scale foundation model pre-trained on transcriptomics of 100 million human cells.Nature communications · 2025Article
- MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.Oncogene · 2023Article
- Novel cytological model for the identification of early oral cancer diagnostic markers: The carcinoma sequence model.Oncology letters · 2022Article
- PBRM1 loss in kidney cancer unbalances the proximal tubule master transcription factor hub to repress proximal tubule differentiation.Cell reports · 2021Article
- MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.Journal of hematology & oncology · 2021Review
- Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27.Scientific reports · 2019Article
- GATA4 loss of function in liver cancer impedes precursor to hepatocyte transition.The Journal of clinical investigation · 2017Article
- p27Kip1, PCAF and PAX5 cooperate in the transcriptional regulation of specific target genes.Nucleic acids research · 2017Article
- Transcriptome analysis of dominant-negative Brd4 mutants identifies Brd4-specific target genes of small molecule inhibitor JQ1.Scientific reports · 2017Article
- BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis.Nature communications · 2016Article
- Functional interactions among members of the MAX and MLX transcriptional network during oncogenesis.Biochimica et biophysica acta · 2015Review
- Exogenous c-Myc Blocks Differentiation and Improves Expansion of Human Erythroblasts In vitro.International journal of stem cells · 2014Article
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- MYC, a downstream target of BRD-NUT, is necessary and sufficient for the blockade of differentiation in NUT midline carcinoma.Oncogene · 2014Article
- p27kip1 maintains a subset of leukemia stem cells in the quiescent state in murine MLL-leukemia.Molecular oncology · 2013Article
- MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1.).Oncogene · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of differentiation has been proposed as an important mechanism for Myc-induced tumorigenesis, but the mechanisms involved are unclear. We have established a genetically defined differentiation model in human leukemia K562 cells by conditional expression of the cyclin-dependent kinase (Cdk) inhibitor p27 (inducible by Zn(2+)) and Myc (activatable by 4-hydroxy-tamoxifen). Induction of p27 resulted in erythroid differentiation, accompanied by Cdk inhibition and G(1) arrest. Interestingly, activation of Myc inhibited p27-mediated erythroid differentiation without affecting p27-mediated proliferation arrest. Microarray-based gene expression indicated that, in the presence of p27, Myc blocked the upregulation of several erythroid-cell-specific genes, including NFE2, JUNB, and GATA1 (transcription factors with a pivotal role in erythropoiesis). Moreover, Myc also blocked the upregulation of Mad1, a transcriptional antagonist of Myc that is able to induce erythroid differentiation. Cotransfection experiments demonstrated that Myc-mediated inhibition of differentiation is partly dependent on the repression of Mad1 and GATA1. In conclusion, this model demonstrates that Myc-mediated inhibition of differentiation depends on the regulation of a specific gene program, whereas it is independent of p27-mediated cell cycle arrest. Our results support the hypothesis that differentiation inhibition is an important Myc tumorigenic mechanism that is independent of cell proliferation.
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