|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 13, 9314-9323, March 31, 2000
From the Induction of apoptosis in a variety of cell types
leads to inhibition of protein synthesis. Recently, the cleavage of
eukaryotic translation initiation factor 4G (eIF4G) by caspase 3 was
described as a possible event contributing to translation inhibition.
Here, we report the cleavage of another initiation factor in apoptotic cells, eIF2
Identification of Caspase 3-mediated Cleavage and Functional
Alteration of Eukaryotic Initiation Factor 2
in Apoptosis*
,
**
Department of Microbiology, University of
Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, the
§ Department of Biochemistry and Molecular Biology, Oklahoma
State University, Stillwater, Oklahoma 74078, the ¶ Department of
Developmental Biology, University of Utrecht, 3584 CH Utrecht, The
Netherlands, and the Department of Molecular Virology and
Microbiology, Baylor College of Medicine, Houston, Texas 77030
, that could contribute to regulation of translation during apoptosis. This cleavage event could be completely inhibited by
pretreatment of HeLa cells with Z-VAD-fmk. In vitro
analysis using purified eIF2 and purified caspases showed cleavage of
eIF2 by caspase 3, 6, 8, and 10 but not 9. Caspase 3 most
efficiently cleaved eIF2 and this could be inhibited by addition of
Ac-DEVD-CHO in vitro. Comparison of cleavage of
phosphorylated versus nonphosphorylated eIF2 revealed a
modest preference of the caspases for the nonphosphorylated form. When
eIF2·2B complex was used as substrate, only caspase 3 was capable of
eIF2 cleavage, which was not affected by phosphorylation of the subunit. The eIF2·GDP binary complex was cleaved much less
efficiently by caspase 3. Sequence analysis of the cleavage fragment
suggested that the cleavage site is located in the C-terminal portion
of the protein. Analysis showed that after caspase cleavage, exchange
of GDP bound to eIF2 was very rapid and no longer dependent upon eIF2B.
Furthermore, in vitro translation experiments indicated that cleavage of eIF2 results in functional alteration of the eIF2
complex, which no longer stimulated upstream AUG selection on a
mRNA containing a viral internal ribosome entry site and was no
longer capable of stimulating overall translation. In conclusion, we
describe here the cleavage of a translation initiation factor, eIF2
that could contribute to inhibition or alteration of protein synthesis
during the late stages of apoptosis.
*
This work was supported by National Institutes of Health
Grants AI27914 and GM59803 (to R. E. L.), Oklahoma
Agricultural Experiment Station project number 1975, and NIEHS,
National Institutes of Health Grant ES 042299 (to R. L. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. M. Schewe and J. A. Aguirre-Ghiso Inhibition of eIF2{alpha} Dephosphorylation Maximizes Bortezomib Efficiency and Eliminates Quiescent Multiple Myeloma Cells Surviving Proteasome Inhibitor Therapy Cancer Res., February 15, 2009; 69(4): 1545 - 1552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Rizos, H. A. McKenzie, A. L. Ayub, S. Woodruff, T. M. Becker, L. L. Scurr, J. Stahl, and R. F. Kefford Physical and Functional Interaction of the p14ARF Tumor Suppressor with Ribosomes J. Biol. Chem., December 8, 2006; 281(49): 38080 - 38088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tomita, Y. Kotake, and R. E. Anderson Mechanism of Protection from Light-Induced Retinal Degeneration by the Synthetic Antioxidant Phenyl-N-tert-Butylnitrone Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 427 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Orton, J. Ling, A. J. Waskiewicz, J. A. Cooper, W. C. Merrick, N. L. Korneeva, R. E. Rhoads, N. Sonenberg, and J. A. Traugh Phosphorylation of Mnk1 by Caspase-activated Pak2/{gamma}-PAK Inhibits Phosphorylation and Interaction of eIF4G with Mnk J. Biol. Chem., September 10, 2004; 279(37): 38649 - 38657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. VAN EDEN, M. P. BYRD, K. W. SHERRILL, and R. E. LLOYD Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress RNA, March 1, 2004; 10(3): 469 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-C. Suen, M.-S. Yu, K.-F. So, R. C.-C. Chang, and J. Hugon Upstream Signaling Pathways Leading to the Activation of Double-stranded RNA-dependent Serine/Threonine Protein Kinase in {beta}-Amyloid Peptide Neurotoxicity J. Biol. Chem., December 12, 2003; 278(50): 49819 - 49827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Pakay, A. A. Hobbs, S. R. Kimball, and M. Guppy The role of eukaryotic initiation factor 2{alpha} during the metabolic depression associated with estivation J. Exp. Biol., July 15, 2003; 206(14): 2363 - 2371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. W. Jeffrey, M. Bushell, V. J. Tilleray, S. Morley, and M. J. Clemens Inhibition of Protein Synthesis in Apoptosis: Differential Requirements by the Tumor Necrosis Factor {alpha} Family and a DNA-damaging Agent for Caspases and the Double-stranded RNA-dependent Protein Kinase Cancer Res., April 1, 2002; 62(8): 2272 - 2280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Tee and C. G. Proud Caspase Cleavage of Initiation Factor 4E-Binding Protein 1 Yields a Dominant Inhibitor of Cap-Dependent Translation and Reveals a Novel Regulatory Motif Mol. Cell. Biol., March 15, 2002; 22(6): 1674 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zamora, W. E. Marissen, and R. E. Lloyd Multiple eIF4GI-Specific Protease Activities Present in Uninfected and Poliovirus-Infected Cells J. Virol., January 1, 2002; 76(1): 165 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Saelens, M. Kalai, and P. Vandenabeele Translation Inhibition in Apoptosis. CASPASE-DEPENDENT PKR ACTIVATION AND eIF2-alpha PHOSPHORYLATION J. Biol. Chem., November 2, 2001; 276(45): 41620 - 41628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. U.T. Hellen and P. Sarnow Internal ribosome entry sites in eukaryotic mRNA molecules Genes & Dev., July 1, 2001; 15(13): 1593 - 1612. [Full Text] [PDF]
|
|
|
|
|
|
M. Bushell, W. Wood, G. Carpenter, V. M. Pain, S. J. Morley, and M. J. Clemens Disruption of the Interaction of Mammalian Protein Synthesis Eukaryotic Initiation Factor 4B with the Poly(A)-binding Protein by Caspase- and Viral Protease-mediated Cleavages J. Biol. Chem., June 22, 2001; 276(26): 23922 - 23928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Shalak, M. Kaminska, R. Mitnacht-Kraus, P. Vandenabeele, M. Clauss, and M. Mirande The EMAPII Cytokine Is Released from the Mammalian Multisynthetase Complex after Cleavage of Its p43/proEMAPII Component J. Biol. Chem., June 22, 2001; 276(26): 23769 - 23776. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |