p53 and DNA-dependent protein kinase catalytic subunit independently function in regulating actin damage-induced tetraploid G1 arrest

被引:7
|
作者
Chae, Hee-Don [1 ]
Kim, So Youn [1 ]
Park, Sang Eun [1 ]
Kim, Jeongbin [1 ]
Shin, Deug Y. [1 ]
机构
[1] Dankook Univ, Coll Med, Dept Microbiol & Immunol, Cheonan 330714, South Korea
来源
EXPERIMENTAL AND MOLECULAR MEDICINE | 2012年 / 44卷 / 03期
关键词
actin cytoskeleton; ataxia telangiectasia mutated protein; DNA-activated protein kinase; pectenotoxin; 2; tumor suppressor protein p53; P53-DEFICIENT TUMORS; MEDIATED APOPTOSIS; CELL-DEATH; CHECKPOINT; PHOSPHORYLATION; INHIBITION; ACTIVATION; SENESCENCE; EXPRESSION; BCL-X(L);
D O I
10.3858/emm.2012.44.3.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously reported that the p53 tumor suppressor protein plays an essential role in the induction of tetraploid G1 arrest in response to perturbation of the actin cytoskeleton, termed actin damage. In this study, we investigated the role of p53, ataxia telangiectasia mutated protein (ATM), and catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in tetraploid G1 arrest induced by actin damage. Treatment with actin-damaging agents including pectenotoxin-2 (PTX-2) increases phosphorylation of Ser-15 and Ser-37 residues of p53, but not Ser-20 residue. Knockdown of ATM and DNA-PKcs do not affect p53 phosphorylation induced by actin damage. However, while ATM knockdown does not affect tetraploid G1 arrest, knockdown of DNA-PKcs not only perturbs tetraploid G1 arrest, but also results in formation of polyploidy and induction of apoptosis. These results indicate that DNA-PKcs is essential for the maintenance of actin damage induced-tetraploid G1 arrest in a p53-independent manner. Furthermore, actin damage-induced p53 expression is not observed in cells synchronized at G1/S of the cell cycle, implying that p53 induction is due to actin damage-induced tetraploidy rather than perturbation of actin cytoskeleton. Therefore, these results suggest that p53 and DNA- PKcs independently function for tetraploid G1 arrest and preventing polyploidy formation.
引用
收藏
页码:236 / 240
页数:5
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