Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin

Apoptosis. 2007 Jul;12(7):1129-42. doi: 10.1007/s10495-006-0049-1.


Livin is a member of the Inhibitor of Apoptosis Protein family which inhibits apoptosis induced by a variety of stimuli. We previously identified Livin and demonstrated that following apoptotic stimuli, Livin is cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. In the present study, we reveal that while full-length Livin shows diffuse cytoplasmic localization, truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization to the Golgi apparatus. Using mutation analysis, we identified two domains that are crucial for the pro-apoptotic activity of tLivin: the N-terminal region of tLivin which is exposed by cleavage, and the RING domain. We demonstrate that, of the N-terminal sequence, only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin. However, while the perinuclear localization of tLivin is essential, it is not sufficient for tLivin to exert its pro-apoptotic function. Once tLivin is properly localized, an intact RING domain enables its pro-apoptotic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / isolation & purification
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspases / metabolism
  • Cell Line
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism*
  • Golgi Apparatus / metabolism*
  • Humans
  • Inhibitor of Apoptosis Proteins / chemistry
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / isolation & purification
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / metabolism*
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Sequence Alignment
  • Structure-Activity Relationship
  • Transfection


  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • Protein Isoforms
  • Caspases