Our hosting provider will be performing UPS maintenance on Tuesday, Oct 25, 2016 between 8 AM and 5 PM PDT. SciCrunch searching services will be down during this time.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

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

The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis.


In the present study, we demonstrate that a human homologue of Ufd2p (a yeast protein that catalyses the formation of long polyubiquitin chains, and is implicated in responses to environmental stress), UFD2 (ubiquitin fusion degradation protein-2), is cleaved during apoptosis induced by multiple stimuli, including UVB irradiation, Fas ligation, staurosporine treatment and cytotoxic lymphocyte granule-induced death. Caspase 6 and granzyme B efficiently cleave UFD2 [k(cat)/K(m)=(4-5) x 10(4) M(-1) x s(-1)] at Asp(123), whereas caspases 3 and 7 cleave UFD2 approx. 10-fold less efficiently immediately upstream at Asp(109). Thus UFD2 is added to the growing list of proteins with closely spaced caspase and granzyme B cleavage sites, suggesting the presence of a previously unrecognized, conserved motif. Both cleavage sites are contained and conserved within a novel 300-amino-acid N-terminal domain present in apparent UFD2 orthologues in mice and zebrafish, but absent in all UFD2 family members in lower eukaryotes. Full-length recombinant UFD2 exhibited ubiquitin-protein ligase ('E3')-like ubiquitination activity in vitro, but this activity was abolished in recombinant UFD2 truncated at the granzyme B/caspase 6 cleavage site. Cleavage of UFD2 by caspases or granzyme B within this putative regulatory N-terminal domain might have important functional consequences within the apoptotic cascade.

Pubmed ID: 11802788


  • Mahoney JA
  • Odin JA
  • White SM
  • Shaffer D
  • Koff A
  • Casciola-Rosen L
  • Rosen A


The Biochemical journal

Publication Data

February 1, 2002

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR44684
  • Agency: NIDCR NIH HHS, Id: DE12354
  • Agency: NIGMS NIH HHS, Id: GM52597
  • Agency: NIDDK NIH HHS, Id: T32DK07832

Mesh Terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoptosis
  • Baculoviridae
  • Binding Sites
  • Blotting, Northern
  • Caspase 6
  • Caspases
  • Cloning, Molecular
  • Enzyme Inhibitors
  • Fungal Proteins
  • Granzymes
  • HeLa Cells
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases
  • Staurosporine
  • Tissue Distribution
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Ultraviolet Rays