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A death-associated protein kinase (DAPK)-interacting protein, DIP-1, is an E3 ubiquitin ligase that promotes tumor necrosis factor-induced apoptosis and regulates the cellular levels of DAPK.

Death-associated protein kinase (DAPK) is a multi-domain Ser/Thr protein kinase with an important role in apoptosis regulation. In these studies we have identified a DAPK-interacting protein called DIP-1, which is a novel multi-RING finger protein. The RING finger motifs of DIP-1 have E3 ligase activity that can auto-ubiquitinate DIP-1 in vitro. In vivo, DIP-1 is detected as a polyubiquitinated protein, suggesting that the intracellular levels of DIP-1 are regulated by the ubiquitin-proteasome system. Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation.

Pubmed ID: 12351649


  • Jin Y
  • Blue EK
  • Dixon S
  • Shao Z
  • Gallagher PJ


The Journal of biological chemistry

Publication Data

December 6, 2002

Associated Grants

  • Agency: NHLBI NIH HHS, Id: R01 HL054118
  • Agency: NHLBI NIH HHS, Id: R01 HL054118-04
  • Agency: NHLBI NIH HHS, Id: R01HL54118

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Blotting, Northern
  • Blotting, Western
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Cloning, Molecular
  • Cysteine Endopeptidases
  • Death-Associated Protein Kinases
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Fungal Proteins
  • Gene Expression Regulation, Enzymologic
  • HeLa Cells
  • Humans
  • Ligases
  • Mice
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Precipitin Tests
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Time Factors
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha
  • Two-Hybrid System Techniques
  • Ubiquitin
  • Ubiquitin-Protein Ligases