Cleavage of eukaryotic translation initiation factor 4GII correlates with translation inhibition during apoptosis

Marissen, Wilfred Ε.; Gradi, Alessandra; Sonenberg, Nahum; Lloyd, Richard E.

doi:10.1038/sj.cdd.4400750

Cited by 71 publications

(73 citation statements)

References 33 publications

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“…On the other hand, factors that are closely related to complex consists of two subunits, 40S and 60S, each of the translation reaction have been shown to undergo degrawhich contains a large number of proteins and RNA. Al-dation in apoptotic cells: eukaryotic translation initiation factors eIF2, eIF3, eIF4B, and eIF4G are degraded in a 1 This study was supported by Grante-in-Aid for Scientific Research manner dependent on caspases (2,4,8,9). The loss of sucĥ m <^L "^T^^r th6 K• P T°t i°n f ^T^ a q T nt ^ Actors explains, at least in part, the decrease in the rate of…”

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confidence: 99%

Structural Change of Ribosomes during Apoptosis: Degradation and Externalization of Ribosomal Proteins in Doxorubicin-Treated Jurkat Cells

Nishida

Shiratsuchi

Nadano

et al. 2002

Journal of Biochemistry

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Changes in the amount and localization of human ribosomal proteins during apoptosis were determined. When total lysates of Jurkat cells undergoing apoptosis induced by doxorubicin were analyzed by Western blotting, degradation of three ribosomal proteins, S18, L5, and L14, was detected at 48 h after the induction of apoptosis. Decreases in the amounts of these three ribosomal proteins were also observed in ribosome-enriched fractions. These changes were partly abolished by the addition of the pan-caspase inhibitor z-VAD-fmk. Moreover, formation of the 80S ribosome complex appeared to be inhibited at 48 h after apoptosis induction. On the other hand, the rate of protein synthesis, assessed by measuring the incorporation of [ 38 S]Met into bulk proteins, decreased as early as 12 h after the addition of doxorubicin. These results indicate that changes in the amount of ribosomal proteins and the overall structure of ribosomes in apoptosing cells occur after protein synthesis declines. Finally, analyses by flow cytometry, immunofluorescence, and Western blotting showed that six ribosomal proteins, S15, PO, L5, L6, L36a, and L41, were relocalized and expressed at the cell surface during apoptosis. The above results collectively indicate that ribosomes are structurally altered in apoptotic cells following inactivation of protein synthesis.Key words: apoptosis, protein degradation, protein synthesis, ribosomal protein, ribosome.Degradation of chromosomal DNA at the last stage in the though the precise function of individual ribosomal proteins process of apoptosis should result in the complete cessation and RNA has not yet been clarified, it is reasonable to of gene expression in cells fated to die. However, the rate of expect that the inhibition of protein synthesis in apoptotic protein synthesis decreases even before chromosomal DNA cells is the consequence of structural modification of these is degraded (1^1), suggesting the presence of an active molecules. In fact, the 28S ribosomal RNA is selectively mechanism that inhibits gene expression at the level of degraded in apoptotic cells (3,(5)(6)(7). This event occurs at relprotein synthesis in apoptotic cells. The molecular basis for atively early stages of apoptosis via both caspase-depenthis event, however, is not fully understood. dent and -independent mechanisms. It is, however, not A variety of proteins and nucleic acids are involved in clear whether degradation of the 28S RNA leads to strucprotein synthesis. The ribosome stands at the center of the tural changes of ribosomes or the inhibition of protein syntranslational machinery, and the eukaryotic 80S ribosome thesis. On the other hand, factors that are closely related to complex consists of two subunits, 40S and 60S, each of the translation reaction have been shown to undergo degrawhich contains a large number of proteins and RNA. Al-dation in apoptotic cells: eukaryotic translation initiation factors eIF2, eIF3, eIF4B, and eIF4G are degraded in a 1 This study was supported by Grante-in-Aid for Scientific Rese...

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confidence: 99%

Structural Change of Ribosomes during Apoptosis: Degradation and Externalization of Ribosomal Proteins in Doxorubicin-Treated Jurkat Cells

Nishida

Shiratsuchi

Nadano

et al. 2002

Journal of Biochemistry

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“…17 Interestingly, various components of the translation machinery are also direct targets for caspases during apoptosis. [19][20][21] This special issue of CDD, which is devoted to translation control during different types of stress conditions, will highlight several scenarios where specific components of the translation initiation machinery are being modified by caspasemediated proteolysis. In the context of the present chapter, we will focus on the translation initiation factor DAP5/p97, which has a central role during cell death and displays interesting crossinteractions with caspases.…”

Section: Pcd Displays Diversity In Cellular Phenotypes and In The Undmentioning

confidence: 99%

“…These include caspase-mediated processing and inactivation of different initiation factors such as eIF4B, eIF3/p35, eIF2a, eIF4GI and eIF4GII. 9,19,21,55 In addition, it has been documented that PKR kinase is activated by caspases and further inhibits translation initiation by phosphorylating eIF2a. 56 Also, some apoptotic settings involve changes in the phosphorylation state of eIF4E and 4E-BP1, which has a negative impact on protein synthesis.…”

Section: Switching the Initiation Of Protein Synthesis From Cap-depenmentioning

confidence: 99%

“…The truncated DAP5/p86 is a functional translation factor, which supports its own translation through the IRES element within its 5 0 UTR and independently of the 5 0 cap structure. Furthermore, it was demonstrated that stimulation of DAP5 IRES requires active DAP5 protein, since applying the DAP5 dominant-negative fragment (the 20 Marissen et al, 21 Craig et al 65 and Henis-Korenblit et al 71 Ct tail -C-terminal tail of DAP5/p97 miniprotein isolated in the genetic screen) diminished IRESmediated translation in the in-vitro translation system. 68 Thus, it was confirmed that this self-regulatory event generates a positive feedback loop on DAP5 translation in the dying cell, and allows preferential and continuous production of DAP5 protein under the stress-associated translational block.…”

Section: Dap5 Regulation and Function In Pcdmentioning

confidence: 99%

“…As was mentioned in the introduction, it was documented that both eIF4GI and eIF4GII are processed by the executioner caspase-3. [19][20][21]73,74 A consequence of these cleavage events is the complete elimination of the full-length proteins, which may contribute to the sharp reduction in cap-dependent translation. Yet, the appearance of a single stable protein fragment corresponding to the middle portion of eIF4GI, designated eIF4GI M-FAG/p76, was also noticed 19,74 ( Figure 2).…”

Section: Identification Of Dap5 Mrna Targetsmentioning

confidence: 99%

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DAP5 and IRES-mediated translation during programmed cell death

Marash

Kimchi

2005

Cell Death Differ

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DAP5 (Death Associated Protein 5), also named p97 and NAT1, is a member of the eIF4G family that lacks the eIF4E binding site. Its function was linked to programmed cell death (PCD) based on the seminal finding that a fragment of DAP5/ p97 protein, which acted in a dominant-negative manner, protected against IFN-gamma (IFN-g)-induced cell death. Subsequently, it was found that DAP5 protein is activated during cell death by caspase cleavage, yielding a C-terminaltruncated protein of 86 kDa. The p86 form promotes internal ribosome entry site (IRES)-dependent translation of several mRNAs including Apaf-1, c-myc, XIAP, HIAP2 and DAP5 itself, which carries an IRES element in its 5 0 UTR. The activation of DAP5 IRES creates a positive feedback loop, which results in sustained translation of DAP5 protein during PCD under conditions of reduced cap-dependent translation. DAP5 deficiency prevents embryonic stem (ES) cell differentiation, suggesting a wider range of DAP5 mRNA targets and additional mechanisms that might activate the protein.

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Translational control of the proteome: Relevance to cancer

Dua

Williams

2001

Proteomics

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Translational control is an important but relatively unappreciated mechanism that regulates levels of protein products. In addition to a global translational control that regulates the cell's response to external stimuli such as growth factors, cytokines, stress and viral infections, selective translational control has recently been demonstrated to affect many genes related to growth and apoptotic processes. Modifications in the 5'untranslated region of these specific mRNAs may lead to an up-regulation of the protein product by as much as 100-fold. Translational infidelity has been reported in some human cancers for oncogenes such as c-myc and mdm2. Furthermore, modulation of selective translational control has also been demonstrated in cells over-expressing the translation initiation factor elF4E. Elevated levels of elF4E were found in a broad spectrum of solid tumors (breast, head and neck, colon and bladder carcinomas as well as in non-Hodgkin's lymphomas). Other translation initiation factors and translation components such as elongation factors and ribosomal proteins have also been reported to be overexpressed in some human tumors. This review discusses the relevance of these observations to a cell's proteome and for tumorigenesis and how the genomics and proteomics can be used to advance our understanding of the role of translational control in cancer.

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Cleavage of eukaryotic translation initiation factor 4GII correlates with translation inhibition during apoptosis

Cited by 71 publications

References 33 publications

Structural Change of Ribosomes during Apoptosis: Degradation and Externalization of Ribosomal Proteins in Doxorubicin-Treated Jurkat Cells

Structural Change of Ribosomes during Apoptosis: Degradation and Externalization of Ribosomal Proteins in Doxorubicin-Treated Jurkat Cells

DAP5 and IRES-mediated translation during programmed cell death

Translational control of the proteome: Relevance to cancer

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