ArticleThe Journal of clinical investigation2023
TP63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Systematic mapping and in silico reevaluation of genomic copy number variations in primary ovarian insufficiency.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- N-acetylcysteine supplementation improves endocrine-metabolism profiles and ovulation induction efficacy in polycystic ovary syndrome.Journal of ovarian research · 2024Trial
- A Novel BIRC6 Variant Impairs Apoptotic Regulation in Familial Premature Ovarian Insufficiency: Functional Validation in a CRISPR/Cas9 Zebrafish Model.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytes.Cell death discovery · 2026Article
- Transcriptional repression of reaper by Stand still ensures female germline development in Drosophila.PLoS genetics · 2026Article
- From Genes to Lives: Integrating the Complexities of Primary Ovarian Insufficiency.International journal of molecular sciences · 2026Review
- Article
- A TAp63alpha truncating variant associated with primary ovarian insufficiency lowers the cellular apoptotic rate.Journal of ovarian research · 2025Article
- Article
- Synergistic inhibition of TNBC by USP33 and TAP63 through autophagy and ferroptosis activation.Cellular and molecular life sciences : CMLS · 2025Article
- The risk factors, pathogenesis and treatment of premature ovarian insufficiency.Journal of ovarian research · 2025Review
- Integrated multi-omics analysis identifies TLR4-mediated mechanisms in ATBC-induced ovarian dysfunction and female infertility: A network toxicology, transcriptomic, and Mendelian randomization study.Journal of ovarian research · 2025Article
- Identification of genetically engineered strategies to manipulate nano-platforms presenting immunotherapeutic ligands for alleviating primary ovarian insufficiency progression.Cell communication and signaling : CCS · 2025Article
- Mitochondrial Quality Control in Ovarian Function: From Mechanisms to Therapeutic Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.Cell death and differentiation · 2025Article
- Extensive homologous recombination safeguards oocyte genome integrity in mammals.Nucleic acids research · 2025Article
- p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer.Cells · 2025Review
- Novel variants associated with premature ovarian insufficiency in Russian adolescents.Frontiers in endocrinology · 2025Article
- Identification of novel variants underlying non-syndromic primary ovarian insufficiency using a targeted NGS gene panel.Frontiers in endocrinology · 2025Article
- Targeting programmed cell death with natural products: a potential therapeutic strategy for diminished ovarian reserve and fertility preservation.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor p63 guards genome integrity in the female germline, and its mutations have been reported in patients with premature ovarian insufficiency (POI). However, the precise contribution of the TP63 gene to the pathogenesis of POI needs to be further determined. Here, in 1,030 Chinese patients with POI, we identified 6 heterozygous mutations of the TP63 gene that impaired the C-terminal transactivation-inhibitory domain (TID) of the TAp63α protein and resulted in tetramer formation and constitutive activation of the mutant proteins. The mutant proteins induced cell apoptosis by increasing the expression of apoptosis-inducing factors in vitro. We next introduced a premature stop codon and selectively deleted the TID of TAp63α in mice and observed rapid depletion of the p63+/ΔTID mouse oocytes through apoptosis after birth. Finally, to further verify the pathogenicity of the mutation p.R647C in the TID that was present in 3 patients, we generated p63+/R647C mice and also found accelerated oocyte loss, but to a lesser degree than in the p63+/ΔTID mice. Together, these findings show that TID-related variants causing constitutive activation of TAp63α lead to POI by inducing oocyte apoptosis, which will facilitate the genetic diagnosis of POI in patients and provide a potential therapeutic target for extending female fertility.
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