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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 773 - 782 (10page)
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Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKTmTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, p21Cip1/WAF1 is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of p21Cip1/WAF1. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of p21Cip1/WAF1, leading to H3K9me3 and SAHFs formation.
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참고문헌 (29)
참고문헌 신청
Ait-Si-Ali, S. / 2004 / A Suv39hdependent mechanism for silencing S-phase genes in differentiating but not in cycling cells / EMBO J 23:605~615
Bieging, K. T. / 2014 / Unravelling mechanisms of p53-mediated tumour suppression / Nat. Rev. Cancer 14:359~370
Bosch-Presegue, L. / 2011 / Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection / Mol. Cell 42:210~223
Campisi, J. / 2005 / Senescent cells, tumor suppression, and organismal aging : good citizens, bad neighbors / Cell 120:513~522
Cross, B. / 2011 / Inhibition of p53 DNA binding function by the MDM2 protein acidic domain / J. Biol. Chem 286:16018~16029
Bieging, K. T. / 2014 / Unravelling mechanisms of p53-mediated tumour suppression / Nat. Rev. Cancer 14:359~370
Bosch-Presegue, L. / 2011 / Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection / Mol. Cell 42:210~223
Campisi, J. / 2005 / Senescent cells, tumor suppression, and organismal aging : good citizens, bad neighbors / Cell 120:513~522
Cross, B. / 2011 / Inhibition of p53 DNA binding function by the MDM2 protein acidic domain / J. Biol. Chem 286:16018~16029
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