ArticleThe Journal of biological chemistry2014
Promyelocytic leukemia zinc finger-retinoic acid receptor α (PLZF-RARα), an oncogenic transcriptional repressor of cyclin-dependent kinase inhibitor 1A (p21WAF/CDKN1A) and tumor protein p53 (TP53) genes.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Case report:Frontiers in oncology · 2026Article
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- BTB protein family and human breast cancer: signaling pathways and clinical progress.Journal of cancer research and clinical oncology · 2023Review
- p53 as a unique target of action of cisplatin in acute leukaemia cells.Journal of cellular and molecular medicine · 2022Article
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- BTB/POZ zinc finger protein ZBTB16 inhibits breast cancer proliferation and metastasis through upregulating ZBTB28 and antagonizing BCL6/ZBTB27.Clinical epigenetics · 2020Article
- Trisenox Disrupts MDM2-DAXX-HAUSP Complex and Induces Apoptosis in a Mouse Model of Acute Leukemia.Journal of Cancer · 2020Article
- Molecular mechanisms and pathobiology of oncogenic fusion transcripts in epithelial tumors.Oncotarget · 2019Review
- Trisenox disrupts MDM2-DAXX-HAUSP complex and activates p53, cell cycle regulation and apoptosis in acute leukemia cells.Oncotarget · 2018Article
- Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Promyelocytic leukemia zinc finger-retinoic acid receptor α (PLZF-RARα) is an oncogene transcriptional repressor that is generated by a chromosomal translocation between the PLZF and RARα genes in acute promyelocytic leukemia (APL-type) patients. The molecular interaction between PLZF-RARα and the histone deacetylase corepressor was proposed to be important in leukemogenesis. We found that PLZF-RARα can repress transcription of the p21WAF/CDKN1A gene, which encodes the negative cell cycle regulator p21 by binding to its proximal promoter Sp1-binding GC-boxes 3, 4, 5/6, a retinoic acid response element (RARE), and distal p53-responsive elements (p53REs). PLZF-RARα also acts as a competitive transcriptional repressor of p53, RARα, and Sp1. PLZF-RARα interacts with co-repressors such as mSin3A, NCoR, and SMRT, thereby deacetylating histones Ac-H3 and Ac-H4 at the CDKN1A promoter. PLZF-RARα also interacts with the MBD3-NuRD complex, leading to epigenetic silencing of CDKN1A through DNA methylation. Furthermore, PLZF-RARα represses TP53 and increases p53 protein degradation by ubiquitination, further repressing p21 expression. Resultantly, PLZF-RARα promotes cell proliferation and significantly increases the number of cells in S-phase.
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