The CDKN1B-RB1-E2F1 pathway protects mouse spermatogonial stem cells from genomic damage
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- TANAKA Takashi
- Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
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- KANATSU-SHINOHARA Mito
- Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan Japan Science and Technology Agency, PRESTO, Kyoto 606-8501, Japan
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- SHINOHARA Takashi
- Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
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抄録
Spermatogonial stem cells (SSCs) undergo self-renewal divisions to provide the foundation for spermatogenesis. Although Rb1 deficiency is reportedly essential for SSC self-renewal, its mechanism has remained unknown. Here we report that Rb1 is critical for cell cycle progression and protection of SSCs from DNA double-strand breaks (DSBs). Cultured SSCs depleted of Cdkn1b proliferated poorly and showed diminished expression of CDK4 and RB1, thereby leading to hypophosphorylation of RB1. Rb1 deficiency induced cell cycle arrest and apoptosis in cultured SSCs, which expressed markers for DNA DSBs. This DNA damage is caused by increased E2F1 activity, the depletion of which decreased DNA DSBs caused by Rb1 deficiency. Depletion of Cdkn1a and Bbc3, which were upregulated by Trp53, rescued Rb1-deficient cells from undergoing cell cycle arrest and apoptosis. These results suggest that the CDKN1B-RB1-E2F1 pathway is essential for SSC self-renewal and protects SSCs against genomic damage.
収録刊行物
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- Journal of Reproduction and Development
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Journal of Reproduction and Development 61 (4), 305-316, 2015
公益社団法人 日本繁殖生物学会
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詳細情報 詳細情報について
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- CRID
- 1390282681313755136
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- NII論文ID
- 130005094647
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- NII書誌ID
- AA10936678
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- ISSN
- 13484400
- 09168818
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- HANDLE
- 2433/202104
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- NDL書誌ID
- 026728108
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- PubMed
- 25959802
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可