ArticleMolecular oncology2018
Unscheduled HDAC4 repressive activity in human fibroblasts triggers TP53-dependent senescence and favors cell transformation.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence.Frontiers in aging · 2024Article
- Article
- The Potential of Senescence as a Target for Developing Anticancer Therapy.International journal of molecular sciences · 2023Review
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- HDAC4 degradation during senescence unleashes an epigenetic program driven by AP-1/p300 at selected enhancers and super-enhancers.Genome biology · 2021Article
- Quis Custodiet Ipsos Custodes (Who Controls the Controllers)? Two Decades of Studies on HDAC9.Life (Basel, Switzerland) · 2021Review
- The Histone Code of Senescence.Cells · 2020Review
- Different class IIa HDACs repressive complexes regulate specific epigenetic responses related to cell survival in leiomyosarcoma cells.Nucleic acids research · 2020Article
- Genetic Programs Driving Oncogenic Transformation: Lessons from in Vitro Models.International journal of molecular sciences · 2019Article
- HDAC7-mediated control of tumour microenvironment maintains proliferative and stemness competence of human mammary epithelial cells.Molecular oncology · 2019Article
- ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment.Molecular oncology · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of the class IIa HDACs is frequently altered in different human cancers. In mouse models these transcriptional repressors can trigger transformation, acting as bona fide oncogenes. Whether class IIa HDACs also exhibit transforming activities in human cells is currently unknown. We infected primary human fibroblasts with retroviruses to investigate the transforming activity of HDAC4 in cooperation with well-known oncogenes. We have discovered that HDAC4 triple mutant (S246A, S467A, S632A) (HDAC4-TM), a nuclear resident version of the deacetylase, triggers TP53 stabilization and OIS (oncogene-induced senescence). Unlike RAS, HDAC4-induced OIS was TP53-dependent and characterized by rapid cell cycle arrest and accumulation of an unusual pattern of γH2AX-positive foci. The inactivation of both TP53 and of the retinoblastoma (pRb) tumor suppressors, as induced by the viral oncogenes large and small T of SV40, triggers anchorage-independent growth in RAS, HDAC4-TM and, to a lesser extent, in HDAC4-wild type (WT)-expressing cells. Our results suggest an oncogenic function of class IIa HDACs in human cells, and justify further efforts to discover and evaluate isoform-specific inhibitors of these epigenetic regulators from a therapeutic perspective.
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