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Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.

Publication ,  Journal Article
Holley, CL; Olson, MR; Colón-Ramos, DA; Kornbluth, S
Published in: Nat Cell Biol
June 2002

Inhibitors of apoptosis (IAPs) inhibit caspases, thereby preventing proteolysis of apoptotic substrates. IAPs occlude the active sites of caspases to which they are bound and can function as ubiquitin ligases. IAPs are also reported to ubiquitinate themselves and caspases. Several proteins induce apoptosis, at least in part, by binding and inhibiting IAPs. Among these are the Drosophila melanogaster proteins Reaper (Rpr), Grim, and HID, and the mammalian proteins Smac/Diablo and Omi/HtrA2, all of which share a conserved amino-terminal IAP-binding motif. We report here that Rpr not only inhibits IAP function, but also greatly decreases IAP abundance. This decrease in IAP levels results from a combination of increased IAP degradation and a previously unrecognized ability of Rpr to repress total protein translation. Rpr-stimulated IAP degradation required both IAP ubiquitin ligase activity and an unblocked Rpr N terminus. In contrast, Rpr lacking a free N terminus still inhibited protein translation. As the abundance of short-lived proteins are severely affected after translational inhibition, the coordinated dampening of protein synthesis and the ubiquitin-mediated destruction of IAPs can effectively reduce IAP levels to lower the threshold for apoptosis.

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Published In

Nat Cell Biol

DOI

ISSN

1465-7392

Publication Date

June 2002

Volume

4

Issue

6

Start / End Page

439 / 444

Location

England

Related Subject Headings

  • Xenopus laevis
  • X-Linked Inhibitor of Apoptosis Protein
  • Transfection
  • Proteins
  • Protein Biosynthesis
  • Protein Binding
  • Peptides
  • Oocytes
  • Molecular Sequence Data
  • Kidney
 

Citation

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Holley, C. L., Olson, M. R., Colón-Ramos, D. A., & Kornbluth, S. (2002). Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nat Cell Biol, 4(6), 439–444. https://doi.org/10.1038/ncb798
Holley, Christopher L., Michael R. Olson, Daniel A. Colón-Ramos, and Sally Kornbluth. “Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.Nat Cell Biol 4, no. 6 (June 2002): 439–44. https://doi.org/10.1038/ncb798.
Holley CL, Olson MR, Colón-Ramos DA, Kornbluth S. Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nat Cell Biol. 2002 Jun;4(6):439–44.
Holley, Christopher L., et al. “Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.Nat Cell Biol, vol. 4, no. 6, June 2002, pp. 439–44. Pubmed, doi:10.1038/ncb798.
Holley CL, Olson MR, Colón-Ramos DA, Kornbluth S. Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nat Cell Biol. 2002 Jun;4(6):439–444.

Published In

Nat Cell Biol

DOI

ISSN

1465-7392

Publication Date

June 2002

Volume

4

Issue

6

Start / End Page

439 / 444

Location

England

Related Subject Headings

  • Xenopus laevis
  • X-Linked Inhibitor of Apoptosis Protein
  • Transfection
  • Proteins
  • Protein Biosynthesis
  • Protein Binding
  • Peptides
  • Oocytes
  • Molecular Sequence Data
  • Kidney