title: Ataxia telangiectasia-mutated- and Rad3-related protein regulates the DNA damage-induced G2/M checkpoint through the Aurora A cofactor Bora protein.
abstract: 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.
authors.affiliation: Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.forename: Bowen
authors.initials: B
authors.lastname: Gao
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Yuan
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lou
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004789:Enzyme Activation / Q000235:genetics / Q000528:radiation effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis / Q000528:radiation effects*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D014982:Xenopus laevis; D000097869:Polo-Like Kinase 1
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D044843:SKP Cullin F-Box Protein Ligases; D000097869:Polo-Like Kinase 1; C528235:bora protein, human; C576597:ATR protein, human
keywords: Cell Biology; Cell Cycle; Checkpoint Control; DNA Damage Response; Protein Degradation