ArticleThe Journal of biological chemistry2012
The histone acetyltransferase TIP60 interacts with c-Myb and inactivates its transcriptional activity in human leukemia.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Post-translational modifications of epigenetic modifier TIP60: their role in cellular functions and cancer.Epigenetics & chromatin · 2025Review
- Review
- MYB: A Key Transcription Factor in the Hematopoietic System Subject to Many Levels of Control.Advances in experimental medicine and biology · 2024Review
- Tip60/Kat5 may be a novel candidate histone acetyltransferase for the regulation of liver iron localization via acetylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Article
- Characterization of the MYB-inhibitory potential of the Pan-HDAC inhibitor LAQ824.BBA advances · 2022Article
- Tip60 might be a candidate for the acetylation of hepatic carbonic anhydrase I and III in mice.Molecular biology reports · 2021Article
- TIP60 up-regulates ΔNp63α to promote cellular proliferation.The Journal of biological chemistry · 2019Article
- The histone variant H2A.Z in gene regulation.Epigenetics & chromatin · 2019Review
- MYB induces the expression of the oncogenic corepressor SKI in acute myeloid leukemia.Oncotarget · 2018Article
- CDK9-mediated phosphorylation controls the interaction of TIP60 with the transcriptional machinery.EMBO reports · 2018Article
- Dual Mechanism ofMolecular and cellular biology · 2017Article
- KATs in cancer: functions and therapies.Oncogene · 2015Review
- The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis.Frontiers in oncology · 2015Review
- Identification of subtype specific miRNA-mRNA functional regulatory modules in matched miRNA-mRNA expression data: multiple myeloma as a case.BioMed research international · 2015Article
- p53 Acetylation: Regulation and Consequences.Cancers · 2014Review
- Review
- Article
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Authors and funding
3 authors.
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Abstract
The histone acetyltransferase TIP60 is a coregulator of transcription factors and is implicated in tumorigenesis. In this study, we explored potential regulatory relationships between TIP60 and the c-Myb oncoprotein in hematopoietic cells. We first showed that TIP60 is a c-Myb interacting protein and that the interaction is dependent on the TIP60 acetyltransferase domain and c-Myb transactivation domain. We then found that coexpressing TIP60 decreases the transcriptional activation ability of c-Myb in functional reporter assays. A ChIP assay also revealed that TIP60 binds to the c-Myb target gene c-Myc promoter in a c-Myb-dependent manner. Consistently, knockdown of Tip60 expression by siRNA increased endogenous c-Myc expression. Furthermore, coimmunoprecipitation of Jurkat cell lysates revealed that c-Myb is associated with histone deacetylases HDAC1 and HDAC2, known to interact with TIP60 and repress transcription. Finally, we compared Tip60 expression in six primary AML samples with three normal CD34(+) cell samples using quantitative RT-PCR. Tip60 expression was significantly (∼60%) lower in the AML samples. In summary, these studies demonstrate that TIP60 negatively modulates c-Myb transcriptional activity by recruiting histone deacetylases in human hematopoietic cells, leading us to hypothesize that TIP60 is a normal regulator of c-Myb function and that dysregulated or mutated TIP60 may contribute to c-Myb-driven leukemogenesis.
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Registered trials
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