Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 99 (8): 5400-5405

Copyright © 2002 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins

Sivan Henis-Korenblit, Gidi Shani, Tal Sines, Lea Marash, Galit Shohat, and Adi Kimchi*

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel

Accepted for publication February 21, 2002.

Received for publication October 22, 2001.

Abstract: Apoptosis is characterized by a translation switch from capdependent to internal ribosome entry site (IRES)-mediated protein translation. During apoptosis, several members of the eukaryotic initiation factor (eIF)4G family are cleaved specifically by caspases. Here we investigated which of the caspase-cleaved eIF4G family members could support cap-independent translation through IRES elements that retain activity in the dying cell. We focused on two major fragments arising from the cleavage of eIF4GI and death-associated protein 5 (DAP5) proteins (eIF4GI M-FAG/p76 and DAP5/p86, respectively), because they are the only potential candidates to preserve the minimal scaffold function needed to mediate translation. Transfection-based experiments in cell cultures indicated that expression of DAP5/p86 in cells stimulated protein translation from the IRESs of c-Myc, Apaf-1, DAP5, and XIAP. In contrast, these IRESs were refractory to the ectopically expressed eIF4GI M-FAG/p76. Furthermore, our study provides in vivo evidence that the caspase-mediated removal of the C-terminal tail of DAP5/p97 relieves an inhibitory effect on the protein's ability to support cap-independent translation through the DAP5 IRES. Altogether, the data suggest that DAP5 is a caspase-activated translation factor that mediates translation through a repertoire of IRES elements, supporting the translation of apoptosis-related proteins.


* To whom reprint requests should be addressed. E-mail: Adi.Kimchi{at}weizmann.ac.il.

Communicated by Leo Sachs, Weizmann Institute of Science, Rehovot, Israel


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator.
S. Bradley, S. Narayanan, and M. Rosbash (2012)
Genetics 192, 943-957
   Abstract »    Full Text »    PDF »
PDGF enhances IRES-mediated translation of Laminin B1 by cytoplasmic accumulation of La during epithelial to mesenchymal transition.
M. Petz, N. C. C. Them, H. Huber, and W. Mikulits (2012)
Nucleic Acids Res. 40, 9738-9749
   Abstract »    Full Text »    PDF »
GPR41 Gene Expression Is Mediated by Internal Ribosome Entry Site (IRES)-dependent Translation of Bicistronic mRNA Encoding GPR40 and GPR41 Proteins.
K. Bahar Halpern, A. Veprik, N. Rubins, O. Naaman, and M. D. Walker (2012)
J. Biol. Chem. 287, 20154-20163
   Abstract »    Full Text »    PDF »
eIF2{alpha} Phosphorylation Tips the Balance to Apoptosis during Osmotic Stress.
E. Bevilacqua, X. Wang, M. Majumder, F. Gaccioli, C. L. Yuan, C. Wang, X. Zhu, L. E. Jordan, D. Scheuner, R. J. Kaufman, et al. (2010)
J. Biol. Chem. 285, 17098-17111
   Abstract »    Full Text »    PDF »
Evolutionary changes in the Leishmania eIF4F complex involve variations in the eIF4E-eIF4G interactions.
Y. Yoffe, M. Leger, A. Zinoviev, J. Zuberek, E. Darzynkiewicz, G. Wagner, and M. Shapira (2009)
Nucleic Acids Res. 37, 3243-3253
   Abstract »    Full Text »    PDF »
The eIF4G homolog DAP5/p97 supports the translation of select mRNAs during endoplasmic reticulum stress.
S. M. Lewis, S. Cerquozzi, T. E. Graber, N. H. Ungureanu, M. Andrews, and M. Holcik (2008)
Nucleic Acids Res. 36, 168-178
   Abstract »    Full Text »    PDF »
Translational control of the interferon regulatory factor 2 mRNA by IRES element.
D. Dhar, S. Roy, and S. Das (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
The eIF4G-homolog p97 can activate translation independent of caspase cleavage.
M. Nousch, V. Reed, R. J. Bryson-Richardson, P. D. Currie, and T. Preiss (2007)
RNA 13, 374-384
   Abstract »    Full Text »    PDF »
After fertilization of sea urchin eggs, eIF4G is post-translationally modified and associated with the cap-binding protein eIF4E.
N. Oulhen, P. Salaun, B. Cosson, P. Cormier, and J. Morales (2007)
J. Cell Sci. 120, 425-434
   Abstract »    Full Text »    PDF »
Searching for IRES.
S. D. Baird, M. Turcotte, R. G. Korneluk, and M. Holcik (2006)
RNA 12, 1755-1785
   Abstract »    Full Text »    PDF »
p97/DAP5 is a ribosome-associated factor that facilitates protein synthesis and cell proliferation by modulating the synthesis of cell cycle proteins.
S. H. Lee and F. McCormick (2006)
EMBO J. 25, 4008-4019
   Abstract »    Full Text »    PDF »
Internal Ribosome Entry Site-mediated Translation of Apaf-1, but Not XIAP, Is Regulated during UV-induced Cell Death.
N. H. Ungureanu, M. Cloutier, S. M. Lewis, N. de Silva, J. D. Blais, J. C. Bell, and M. Holcik (2006)
J. Biol. Chem. 281, 15155-15163
   Abstract »    Full Text »    PDF »
Eukaryotic translation initiation factor 4GI and p97 promote cellular internal ribosome entry sequence-driven translation.
P. Hundsdoerfer, C. Thoma, and M. W. Hentze (2005)
PNAS 102, 13421-13426
   Abstract »    Full Text »    PDF »
Internal initiation of translation of the TrkB mRNA is mediated by multiple regions within the 5' leader.
T. Dobson, A. Minic, K. Nielsen, E. Amiott, and L. Krushel (2005)
Nucleic Acids Res. 33, 2929-2941
   Abstract »    Full Text »    PDF »
Expression of fragments of translation initiation factor eIF4GI reveals a nuclear localisation signal within the N-terminal apoptotic cleavage fragment N-FAG.
M. J. Coldwell, L. Hashemzadeh-Bonehi, T. M. Hinton, S. J. Morley, and V. M. Pain (2004)
J. Cell Sci. 117, 2545-2555
   Abstract »    Full Text »    PDF »
Translational Induction of the Inhibitor of Apoptosis Protein HIAP2 during Endoplasmic Reticulum Stress Attenuates Cell Death and Is Mediated via an Inducible Internal Ribosome Entry Site Element.
D. Warnakulasuriyarachchi, S. Cerquozzi, H. H. Cheung, and M. Holcik (2004)
J. Biol. Chem. 279, 17148-17157
   Abstract »    Full Text »    PDF »
Demonstrating internal ribosome entry sites in eukaryotic mRNAs using stringent RNA test procedures.
M. E. VAN EDEN, M. P. BYRD, K. W. SHERRILL, and R. E. LLOYD (2004)
RNA 10, 720-730
   Abstract »    Full Text »    PDF »
Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress.
M. E. VAN EDEN, M. P. BYRD, K. W. SHERRILL, and R. E. LLOYD (2004)
RNA 10, 469-481
   Abstract »    Full Text »    PDF »
Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce cell cycle progression through the synthesis of c-Myc protein by internal ribosome entry site-mediated translation via phosphatidylinositol 3-kinase pathway in human factor-dependent leukemic cells.
N. Kobayashi, K. Saeki, and A. Yuo (2003)
Blood 102, 3186-3195
   Abstract »    Full Text »    PDF »
Distinct Regulation of Internal Ribosome Entry Site-mediated Translation following Cellular Stress Is Mediated by Apoptotic Fragments of eIF4G Translation Initiation Factor Family Members eIF4GI and p97/DAP5/NAT1.
T. A. Nevins, Z. M. Harder, R. G. Korneluk, and M. Holcik (2003)
J. Biol. Chem. 278, 3572-3579
   Abstract »    Full Text »    PDF »
Polypyrimidine tract binding protein and poly r(C) binding protein 1 interact with the BAG-1 IRES and stimulate its activity in vitro and in vivo.
B. M. Pickering, S. A. Mitchell, J. R. Evans, and A. E. Willis (2003)
Nucleic Acids Res. 31, 639-646
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882