ArticleProceedings of the National Academy of Sciences of the United States of America2002
Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology.Academia biology · 2025Article
- Spatiotemporal Epigenetic Control of the Histone Gene Chromatin Landscape during the Cell Cycle.Critical reviews in eukaryotic gene expression · 2023Article
- Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Cell and Tissue Structure, Function, and Phenotype.Results and problems in cell differentiation · 2022Review
- Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer.Genes, chromosomes & cancer · 2019Review
- RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia.International journal of molecular sciences · 2019Review
- Nuclear organization mediates cancer-compromised genetic and epigenetic control.Advances in biological regulation · 2018Review
- The ubiquitin ligase STUB1 regulates stability and activity of RUNX1 and RUNX1-RUNX1T1.The Journal of biological chemistry · 2017Article
- An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells.Oncotarget · 2017Article
- Role of RUNX1 in hematological malignancies.Blood · 2017Review
- ANTI-MTG16 ANTIBODIES REVEAL MTG16 SUBCELLULAR DISTRIBUTION AND NUCLEOCYTOPLASMIC TRANSPORT IN ERYTHROLEUKEMIA CELLS.Antibody technology journal · 2015Article
- The dynamic architectural and epigenetic nuclear landscape: developing the genomic almanac of biology and disease.Journal of cellular physiology · 2014Review
- A germline point mutation in Runx1 uncouples its role in definitive hematopoiesis from differentiation.Experimental hematology · 2013Article
- Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation.Human molecular genetics · 2010Article
- Transcription factor-mediated epigenetic regulation of cell growth and phenotype for biological control and cancer.Advances in enzyme regulation · 2010Review
- Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network.Cancer research · 2009Article
- Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes.Journal of cellular physiology · 2009Article
- Organization, integration, and assembly of genetic and epigenetic regulatory machinery in nuclear microenvironments: implications for biological control in cancer.Annals of the New York Academy of Sciences · 2009Article
- Transcription-factor-mediated epigenetic control of cell fate and lineage commitment.Biochemistry and cell biology = Biochimie et biologie cellulaire · 2009Review
- The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes.Journal of cell science · 2008Article
- Genetic and epigenetic regulation in nuclear microenvironments for biological control in cancer.Journal of cellular biochemistry · 2008Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Leukemic disease can be linked to aberrant gene expression. This often is the result of molecular alterations in transcription factors that lead to their misrouting within the nucleus. The acute myelogenous leukemia-related fusion protein AML1ETO is a striking example. It originates from a gene rearrangement t(8;21) that fuses the N-terminal part of the key hematopoietic regulatory factor AML1 (RUNX1) to the ETO (MTG8) repressor protein. AML1ETO lacks the intranuclear targeting signal of the wild-type AML1 and is directed by the ETO component to alternate nuclear matrix-associated sites. To understand this aberrant subnuclear trafficking of AML1ETO, we created a series of mutations in the ETO protein. These were characterized biochemically by immunoblotting and in situ by immunofluorescence microscopy. We identified two independent subnuclear targeting signals in the N- and C-terminal regions of ETO that together direct ETO to the same binding sites occupied by AML1ETO. However, each segment alone is targeted to a different intranuclear location. The N-terminal segment contains a nuclear localization signal and the conserved hydrophobic heptad repeat domain responsible for protein dimerization and interaction with the mSin3A transcriptional repressor. The C-terminal segment spans the nervy domain and the zinc finger region, which together support interactions with the corepressors N-CoR and HDACs. Our findings provide a molecular basis for aberrant subnuclear targeting of the AML1ETO protein, which is a principal defect in t(8;21)-related acute myelogenous leukemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.