ArticleLeukemia2012
Direct interaction of PU.1 with oncogenic transcription factors reduces its serine phosphorylation and promoter binding.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Understanding a high-risk acute myeloid leukemia by analyzing the interactome of its major driver mutation.PLoS genetics · 2022Article
- Intrinsic disorder controls two functionally distinct dimers of the master transcription factor PU.1.Science advances · 2020Article
- The role of zinc and its compounds in leukemia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- Differential effects on gene transcription and hematopoietic differentiation correlate with GATA2 mutant disease phenotypes.Leukemia · 2018Article
- PML/RARa inhibits PTEN expression in hematopoietic cells by competing with PU.1 transcriptional activity.Oncotarget · 2016Article
- Nf1 Haploinsufficiency Alters Myeloid Lineage Commitment and Function, Leading to Deranged Skeletal Homeostasis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Article
- PU.1 affects proliferation of the human acute myeloid leukemia U937 cell line by directly regulating MEIS1.Oncology letters · 2015Article
- Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and Gata3.Development (Cambridge, England) · 2013Article
- Targeting the acute promyelocytic leukemia-associated fusion proteins PML/RARα and PLZF/RARα with interfering peptides.PloS one · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The homeostasis of hematopoiesis in the bone marrow is governed by a small number of key transcription factors, including PU.1, GATA-1 and c/EBPα. PU.1, a member of the E-twenty-six family of transcription factors, is indispensable for normal hematopoiesis. Inactivation of PU.1 induces acute leukemia in mice. Recent data suggest that the leukemia-associated fusion protein pro-myelocytic leukemia/retinoic acid receptor alpha (PML/RARα) inhibits PU.1, but the mechanism mediating this inhibition is unclear. Here, we investigated the mechanisms by which the fusion proteins PML/RARα and pro-myelocytic leukemia zinc finger/RARα (PLZF/RARα) (X-RARα) interfere with the function of PU.1. We found that X-RARα proteins functionally inactivate PU.1 by reducing its promoter-binding capacity, resulting in a reduction in PU.1-dependent transcriptional transactivation. In fact, X-RARα proteins directly interact with PU.1, leading to both the sequestration of PU.1 from its target promoters and a reduction in its serine phosphorylation, which is crucial for its promoter binding and transcriptional activity. We found that the functional inactivation of PU.1 could be overcome by the forced overexpression of PU.1 in PML/RARα- or PLZF/RARα-positive murine hematopoietic progenitor cells; evidently, this overexpression rescued the leukemic differentiation block induced by X-RARα proteins. Our data thus provide strong evidence that X-RARα proteins functionally inhibit PU.1, shedding light on the mechanism by which X-RARα proteins induce leukemogenesis.
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Registered trials
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.