p53 modulates radiation sensitivity independent of p21 transcriptional activation.
p53 modulates radiation sensitivity independent of p21 transcriptional activation.
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p53 调节辐射敏感性，与 p21 转录激活无关。
DOI：
10.1097/01.coc.0000139484.51715.5a
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Keng,PeterC
中科院分区：
文献类型：
--
作者：
Mazzatti,DawnJ;Lee,Yi-Jang;Helt,ChristopherE;O'Reilly,MichaelA;Keng,PeterC
细胞对电离辐射(IR)治疗的敏感性是一种复杂的生物现象，它受几个过程的影响，即细胞检测和修复DNA损伤、调节细胞周期分裂和执行细胞凋亡的能力。由于P53肿瘤抑制蛋白参与了这些过程中的每一个过程的调节，因此对野生型P53修复后H1299 P53缺失的人肺癌细胞的辐射敏感性进行了评估。野生型P53在辐射耐药的H1299细胞中的表达恢复了辐射敏感的表型，这种表型不能完全由P53介导的凋亡导致的细胞死亡来解释。此外，我们发现P53仅在细胞周期的G1期改变辐射敏感性，而S和G2/M期细胞不受P53状态的影响。为了探讨P53诱导G1期放射敏感性的机制，我们研究了H1299/P53细胞对IR的G1/S检查点反应。我们发现，由于p21WAF1/Cip1的转录激活，H1299/P53细胞以P53依赖的方式停滞在G1期。为了确定p53诱导的辐射敏感性是否是累积的p21蛋白表达导致的生殖性死亡的结果，我们在H1299亲本细胞中独立地诱导了p21。然而，p21的诱导不足以解释H1299/p53细胞辐射敏感性的增强。综上所述，这些数据表明，P53通过独立于P53介导的p21转录激活和细胞周期停滞的机制来调节细胞周期G1期的辐射敏感性。
Cellular sensitivity to ionizing radiation (IR) treatment is a complex biologic phenomenon that is affected by several processes, namely the ability of the cell to detect and repair DNA damage, regulate cell cycle division, and execute apoptosis. Because the p53 tumor suppressor protein is implicated in the regulation of each of these processes, radiation sensitivity of H1299 p53-null human lung carcinoma cells was evaluated after restoration of wild-type p53. Expression of wild-type p53 in radiation-resistant H1299 cells reinstated a radiation-sensitive phenotype that was not fully explained by cell death resulting from p53-mediated apoptosis. In addition, we show that p53 alters radiation sensitivity only in the G1 phase of the cell cycle, whereas S-and G2/M-phase cells were unaffected by p53 status. To determine the mechanism of p53-induced G1-phase radiation sensitivity, we investigated the G1/S checkpoint response to IR in H1299/p53 cells. We show that H1299/p53 cells arrest in the G1 phase in a p53-dependent manner as a result of transcriptional activation of p21 WAF1/Cip1. To determine if p53-induced radiation sensitivity was the result of a reproductive death from accumulated p21 protein expression, p21 was independently induced in H1299 parental cells. However, induction of p21 was not sufficient to account for the enhanced radiation sensitivity in H1299/p53 cells. Together, these data indicate that p53 modulates radiation sensitivity in the G1 phase of the cell cycle through mechanisms independent of p53-mediated transcriptional activation of p21 and cell cycle arrest.
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影响因子：
10.5
作者：
Kim, JB;Spiegelman, BM
通讯作者：
Spiegelman, BM
DOI：
10.1073/pnas.0509001102
发表时间：
2005-12-13
影响因子：
11.1
作者：
Wang, MY;Orci, L;Unger, RH
通讯作者：
Unger, RH
影响因子：
11.8
作者：
Stahl, A;Evans, JG;Lodish, HF
通讯作者：
Lodish, HF
DOI：
10.1172/jci14955
发表时间：
2002-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
R. Hundal;K. Petersen;Adam Mayerson;P. Randhawa;S. Inzucchi;S. Shoelson;G. Shulman
通讯作者：
R. Hundal;K. Petersen;Adam Mayerson;P. Randhawa;S. Inzucchi;S. Shoelson;G. Shulman
影响因子：
7.7
作者：
Ozawa, K;Miyazaki, M;Ogawa, S
通讯作者：
Ogawa, S