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.
Keywords:
Cell Biology; Cell Cycle; Checkpoint Control; DNA Damage Response; Protein Degradation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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DNA Damage*
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Enzyme Activation / genetics
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Enzyme Activation / radiation effects
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G2 Phase Cell Cycle Checkpoints / genetics
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G2 Phase Cell Cycle Checkpoints / radiation effects*
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Humans
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M Phase Cell Cycle Checkpoints / genetics
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M Phase Cell Cycle Checkpoints / radiation effects*
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Mice
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Polo-Like Kinase 1
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proteolysis / radiation effects*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Rats
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SKP Cullin F-Box Protein Ligases / genetics
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SKP Cullin F-Box Protein Ligases / metabolism
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Ultraviolet Rays*
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Xenopus laevis
Substances
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Cell Cycle Proteins
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Proto-Oncogene Proteins
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bora protein, human
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SKP Cullin F-Box Protein Ligases
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases