ArticleProceedings of the National Academy of Sciences of the United States of America2011
Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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.
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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.
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Who cites it
71 citing papers in PubMed, 111 citations in OpenAlex.
- Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics.International journal of molecular sciences · 2026Review
- Oncogenic role of ERV with therapeutic potential.Frontiers in immunology · 2026Review
- Synergistic inhibition of TNBC by USP33 and TAP63 through autophagy and ferroptosis activation.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Article
- Viral influencers: deciphering the role of endogenous retroviral LTR12 repeats in cellular gene expression.Journal of virology · 2025Review
- Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.Nucleic acids research · 2024Article
- Epigenetic regulation of HERVs: Implications for cancer immunotherapy.Genes & genomics · 2024Review
- Context dependent activity of p63-bound gene regulatory elements.bioRxiv : the preprint server for biology · 2024Article
- Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events.Nature communications · 2024Article
- Transposable elements in mammalian chromatin organization.Nature reviews. Genetics · 2023Review
- Endogenous Caulimovirids: Fossils, Zombies, and Living in Plant Genomes.Biomolecules · 2023Review
- Designed Ankyrin Repeat Proteins as a tool box for analyzing p63.Cell death and differentiation · 2022Article
- Dominant TP63 missense variants lead to constitutive activation and premature ovarian insufficiency.Human mutation · 2022Article
- Transcriptional Regulation of Endogenous Retroviruses and Their Misregulation in Human Diseases.International journal of molecular sciences · 2022Review
- Mammalian genome innovation through transposon domestication.Nature cell biology · 2022Review
- Structural diversity of p63 and p73 isoforms.Cell death and differentiation · 2022Review
- KRAB zinc finger protein ZNF676 controls the transcriptional influence of LTR12-related endogenous retrovirus sequences.Mobile DNA · 2022Article
- Microorganisms as Shapers of Human Civilization, from Pandemics to Even Our Genomes: Villains or Friends? A Historical Approach.Microorganisms · 2021Review
- SMG1 and CDK12 Link ΔNp63α Phosphorylation to RNA Surveillance in Keratinocytes.Journal of proteome research · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
TAp63, but not its homolog p53, eliminates oocytes that suffered DNA damage. An equivalent gene for guarding the male germ line is currently not known. Here we identify hitherto unknown human p63 transcripts with unique 5'-ends derived from incorporated exons upstream of the currently mapped TP63 gene. These unique p63 transcripts are highly and specifically expressed in testis. Their most upstream region corresponds to a LTR of the human endogenous retrovirus 9 (ERV9). The insertion of this LTR upstream of the TP63 locus occurred only recently in evolution and is unique to humans and great apes (Hominidae). A corresponding p63 protein is the sole p63 species in healthy human testis, and is strongly expressed in spermatogenic precursors but not in mature spermatozoa. In response to DNA damage, this human male germ-cell-encoded TAp63 protein (designated GTAp63) is activated by caspase cleavage near its carboxyterminal domain and induces apoptosis. Human testicular cancer tissues and cell lines largely lost p63 expression. However, pharmacological inhibition of histone deacetylases completely restores p63 expression in testicular cancer cells (>3,000-fold increase). Our data support a model whereby testis-specific GTAp63 protects the genomic integrity of the male germ line and acts as a tumor suppressor. In Hominidae, this guardian function was greatly enhanced by integration of an endogenous retrovirus upstream of the TP63 locus that occurred 15 million years ago. By providing increased germ-line stability, this event may have contributed to the evolution of hominids and enabled their long reproductive periods.
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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.