• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


A proteomic analysis of ataxia telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) substrates identifies the ubiquitin-proteasome system as a regulator for DNA damage checkpoints.

ATM (ataxia telangiectasia-mutated) and ATR (ATM-Rad3-related) are proximal checkpoint kinases that regulate DNA damage response (DDR). Identification and characterization of ATM/ATR substrates hold the keys for the understanding of DDR. Few techniques are available to identify protein kinase substrates. Here, we screened for potential ATM/ATR substrates using phospho-specific antibodies against known ATM/ATR substrates. We identified proteins cross-reacting to phospho-specific antibodies in response to DNA damage by mass spectrometry. We validated a subset of the candidate substrates to be phosphorylated in an ATM/ATR-dependent manner in vivo. Combining with a functional checkpoint screen, we identified proteins that belong to the ubiquitin-proteasome system (UPS) to be required in mammalian DNA damage checkpoint control, particularly the G(1) cell cycle checkpoint, thus revealing protein ubiquitylation as an important regulatory mechanism downstream of ATM/ATR activation for checkpoint control.

Pubmed ID: 17478428


  • Mu JJ
  • Wang Y
  • Luo H
  • Leng M
  • Zhang J
  • Yang T
  • Besusso D
  • Jung SY
  • Qin J


The Journal of biological chemistry

Publication Data

June 15, 2007

Associated Grants

  • Agency: NCI NIH HHS, Id: CA84199
  • Agency: NCI NIH HHS, Id: CA98500

Mesh Terms

  • Amino Acid Sequence
  • Antibodies, Phospho-Specific
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle
  • Cell Cycle Proteins
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • HeLa Cells
  • Humans
  • Proteasome Endopeptidase Complex
  • Protein-Serine-Threonine Kinases
  • Proteome
  • Reproducibility of Results
  • Tumor Suppressor Proteins
  • Ubiquitin