TY - JOUR
T1 - Ataxia telangiectasia-mutated- and Rad3-related protein regulates the DNA damage-induced G2/M checkpoint through the Aurora A cofactor Bora protein
AU - Qin, Bo
AU - Gao, Bowen
AU - Yu, Jia
AU - Yuan, Jian
AU - Lou, Zhenkun
PY - 2013/5/31
Y1 - 2013/5/31
N2 - Polo-like kinase1 (Plk1) activation is inhibited in response to DNA damage, and this inhibition contributes to the activation of the G2/M checkpoint, although the molecular mechanism by which Plk1 is inhibited is not clear. Here we report that the DNA damage signaling pathway inhibits Plk1 activity through Bora. Following UV irradiation, ataxia telangiectasia-mutated- and Rad3-related protein phosphorylates Bora at Thr-501. The phosphorylated Thr-501 is subsequently recognized by the E3 ubiquitin ligase SCF-β-TRCP, which targets Bora for degradation. The degradation of Bora compromises Plk1 activation and contributes to DNA damage-induced G2 arrest. These findings shed new light on Plk1 regulation by the DNA damage response pathway.
AB - Polo-like kinase1 (Plk1) activation is inhibited in response to DNA damage, and this inhibition contributes to the activation of the G2/M checkpoint, although the molecular mechanism by which Plk1 is inhibited is not clear. Here we report that the DNA damage signaling pathway inhibits Plk1 activity through Bora. Following UV irradiation, ataxia telangiectasia-mutated- and Rad3-related protein phosphorylates Bora at Thr-501. The phosphorylated Thr-501 is subsequently recognized by the E3 ubiquitin ligase SCF-β-TRCP, which targets Bora for degradation. The degradation of Bora compromises Plk1 activation and contributes to DNA damage-induced G2 arrest. These findings shed new light on Plk1 regulation by the DNA damage response pathway.
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U2 - 10.1074/jbc.M113.456780
DO - 10.1074/jbc.M113.456780
M3 - Article
C2 - 23592782
AN - SCOPUS:84878393360
SN - 0021-9258
VL - 288
SP - 16139
EP - 16144
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -