ArticlePLoS genetics2011
Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- The therapeutic potential of Zuogui Wan in oligoasthenozoospermia: insights from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.Scientific reports · 2025Article
- BMP and STRA8 act collaboratively to ensure correct mitotic-to-meiotic transition in the fetal mouse ovary.Development (Cambridge, England) · 2025Article
- p53 Controls Meiotic Prophase Progression and Crossover Formation.International journal of molecular sciences · 2022Article
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis.Biomolecules · 2021Review
- Testis-specific Arf promoter expression in a transposase-aided BAC transgenic mouse model.Molecular biology reports · 2019Article
- Diverse roles for CDK-associated activity during spermatogenesis.FEBS letters · 2019Review
- Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Dual Role of the Alternative Reading Frame ARF Protein in Cancer.Biomolecules · 2019Review
- Interplay between p53 and Ink4c in spermatogenesis and fertility.Cell cycle (Georgetown, Tex.) · 2018Article
- Article
- Small mitochondrial Arf (smArf) protein corrects p53-independent developmental defects ofProceedings of the National Academy of Sciences of the United States of America · 2017Article
- p53 and TAp63 participate in the recombination-dependent pachytene arrest in mouse spermatocytes.PLoS genetics · 2017Article
- Elimination of p19JCI insight · 2016Article
- Expressions of Sox9, Sox5, and Sox13 transcription factors in mice testis during postnatal development.Molecular and cellular biochemistry · 2015Article
- The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes.PLoS genetics · 2015Article
- Roles of ubiquitination and SUMOylation on prostate cancer: mechanisms and clinical implications.International journal of molecular sciences · 2015Review
- Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis.Molecular oncology · 2014Article
- Repression of the soma-specific transcriptome by Polycomb-repressive complex 2 promotes male germ cell development.Genes & development · 2014Article
- ARF: a versatile DNA damage response ally at the crossroads of development and tumorigenesis.Frontiers in genetics · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The mammalian Cdkn2a (Ink4a-Arf) locus encodes two tumor suppressor proteins (p16(Ink4a) and p19(Arf)) that respectively enforce the anti-proliferative functions of the retinoblastoma protein (Rb) and the p53 transcription factor in response to oncogenic stress. Although p19(Arf) is not normally detected in tissues of young adult mice, a notable exception occurs in the male germ line, where Arf is expressed in spermatogonia, but not in meiotic spermatocytes arising from them. Unlike other contexts in which the induction of Arf potently inhibits cell proliferation, expression of p19(Arf) in spermatogonia does not interfere with mitotic cell division. Instead, inactivation of Arf triggers germ cell-autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production. Arf deficiency also causes premature, elevated, and persistent accumulation of the phosphorylated histone variant H2AX, reduces numbers of chromosome-associated complexes of Rad51 and Dmc1 recombinases during meiotic prophase, and yields incompletely synapsed autosomes during pachynema. Inactivation of Ink4a increases the fraction of spermatogonia in S-phase and restores sperm numbers in Ink4a-Arf doubly deficient mice but does not abrogate γ-H2AX accumulation in spermatocytes or p53-dependent apoptosis resulting from Arf inactivation. Thus, as opposed to its canonical role as a tumor suppressor in inducing p53-dependent senescence or apoptosis, Arf expression in spermatogonia instead initiates a salutary feed-forward program that prevents p53-dependent apoptosis, contributing to the survival of meiotic male germ cells.
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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.