共查询到20条相似文献,搜索用时 31 毫秒
1.
The p53 tumor suppressor is activated in the cellular response to genotoxic stress. Transactivation of p53 target genes dictates cell cycle arrest and DNA repair or induction of apoptosis; however, a molecular mechanism responsible for these distinct functions remains unclear. Recent studies revealed that phosphorylation of p53 on Ser(46) was associated with induction of p53AIP1 expression, resulting in the commitment of the cell fate into apoptotic cell death. Moreover, upon exposure to genotoxic stress, p53DINP1 was expressed and recruited a kinase(s) to p53 that specifically phosphorylated Ser(46). Here, we show that the pro-apoptotic kinase, protein kinase C delta (PKCdelta), is involved in phosphorylation of p53 on Ser(46). PKCdelta-mediated phosphorylation is required for the interaction of PKCdelta with p53. The results also demonstrate that p53DINP1 associates with PKCdelta upon exposure to genotoxic agents. Consistent with these results, PKCdelta potentiates p53-dependent apoptosis by Ser(46) phosphorylation in response to genotoxic stress. These findings indicate that PKCdelta regulates p53 to induce apoptotic cell death in the cellular response to DNA damage. 相似文献
2.
3.
Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage 下载免费PDF全文
Yoshida K Yamaguchi T Shinagawa H Taira N Nakayama KI Miki Y 《Molecular and cellular biology》2006,26(9):3414-3431
DNA topoisomerase II is an essential nuclear enzyme that modulates DNA processes by altering the topological state of double-stranded DNA. This enzyme is required for chromosome condensation and segregation; however, the regulatory mechanism of its activation is largely unknown. Here we demonstrate that topoisomerase IIalpha is activated in response to genotoxic stress. Concomitant with the activation, the expression of topoisomerase IIalpha is increased following DNA damage. The results also demonstrate that the proapoptotic kinase protein kinase C delta (PKCdelta) interacts with topoisomerase IIalpha. This association is in an S-phase-specific manner and is required for stabilization and catalytic activation of topoisomerase IIalpha in response to DNA damage. Conversely, inhibition of PKCdelta activity attenuates DNA damage-induced activation of topoisomerase IIalpha. Finally, aberrant activation of topoisomerase IIalpha by PKCdelta is associated with induction of apoptosis upon exposure to genotoxic agents. These findings indicate that PKCdelta regulates topoisomerase IIalpha and thereby cell fate in the genotoxic stress response. 相似文献
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Safiya Khurshid Shuhua Chen Pia Hasskamp Tamina Seeger‐Nukpezah Katharina Schilberg Lukas Heukamp Tobias Lamkemeyer Martin L Sos Roman K Thomas Drew Lowery Frederik Roels Matthias Fischer Max C Liebau Ulrike Resch Tülay Kisner Fabian Röther Malte P Bartram Roman Ulrich Müller Francesca Fabretti Peter Kurschat Björn Schumacher Matthias Gaestel René H Medema Michael B Yaffe Bernhard Schermer Thomas Benzing 《The EMBO journal》2012,31(20):3961-3975
15.
16.
17.
18.
19.