Cleavage of polypeptide chain initiation factor eIF4GI during apoptosis in lymphoma cells: characterisation of an internal fragment generated by caspase-3-mediated cleavage

Bushell, Martin; Poncet, Didier; Marissen, Wilfred Ε.; Flotow, Horst; Lloyd, Richard E.; Clemens, Mike; Morley, Simon

doi:10.1038/sj.cdd.4400699

Cited by 85 publications

(104 citation statements)

References 47 publications

(69 reference statements)

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“…Additional work will be required to confirm this proposed processing scheme and to identify additional sites that are less efficiently recognized by caspase 3. However, it is very clear that eIF4GII is cleaved into many more fragments by caspase 3 than eIF4GI, 28 which likely destroys any useful function of eIF4GII fragments in translation.…”

Section: Discussionmentioning

confidence: 99%

“…To account for all the dominant fragments observed, we hypothesize eIF4GII is cleaved at all four classical caspase 3 cleavage sites (DxxD) at positions 557 ± 560, 848 ± 851, 975 ± 978 and 1159 ± 1162 plus an additional IESD at position 1407. Recently, the caspase 3 cleavage sites on eIF4GI were identified 28 at positions DLLD 492 A, and DRLD 1136 R (see Figure 9). Although neither of these sites are conserved between eIF4GI and eIF4GII, the potential caspase 3 cleavage sites DPSD 560 L and Figure 9 Proposed processing scheme for eIF4GII.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2000

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Eukaryotic translation initiation factor 4G (eIF4G), which has two homologs known as eIF4GI and eIF4GII, functions in a complex (eIF4F) which binds to the 5' cap structure of cellular mRNAs and facilitates binding of capped mRNA to 40S ribosomal subunits. Disruption of this complex in enterovirusinfected cells through eIF4G cleavage is known to block this step of translation initiation, thus leading to a drastic inhibition of cap-dependent translation. Here, we show that like eIF4GI, the newly identified homolog eIF4GII is cleaved during apoptosis in HeLa cells and can serve as a substrate for caspase 3. Proteolysis of both eIF4GI and eIF4GII occurs with similar kinetics and coincides with the profound translation inhibition observed in cisplatin-treated HeLa cells. Both eIF4GI and eIF4GII can be cleaved by caspase 3 with similar efficiency in vitro, however, eIF4GII is processed into additional fragments which destroy its core central domain and likely contributes to the shutoff of translation observed in

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2000

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“…The proteolytic processing of eIF4GI yields a 76 kDa fragment (referred to as M-FAG for middle fragment of apoptotic cleavage of eIF4GI) that retains binding sites for eIF4E, eIF4A and eIF3 (see Fig. 4, Bushell et al, 2000). The cleavage of eIF4GII has also been described in apoptotic cells.…”

Section: Cleavage Of Eif4g During Apoptosismentioning

confidence: 98%

Conducting the initiation of protein synthesis: the role of eIF4G

Prévot

Darlix

Ohlmann

2003

Biology of the Cell

197

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The eukaryotic initiation factor eIF4G is a large modular protein which serves as a docking site for initiation factors and proteins involved in RNA translation. Together with eIF4E and eIF4A, eIF4G constitutes the eIF4F complex which is a key component in promoting ribosome binding to the mRNA. Thus, the central role of eIF4G in initiation makes it a valid target for events aimed at modulating translation. Such events occur during viral infection by picornaviruses and lentiviruses and result in the hijack of the translational machinery through cleavage of eIF4G. Proteolysis of eIF4G is also mediated by caspases during the onset of apoptosis causing inhibition of protein synthesis. We will review the role of eIF4G and protein partners as well as the cellular and viral events that modulate eIF4G activity in the initiation of translation.

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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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Cleavage of polypeptide chain initiation factor eIF4GI during apoptosis in lymphoma cells: characterisation of an internal fragment generated by caspase-3-mediated cleavage

Cited by 85 publications

References 47 publications

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

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

Conducting the initiation of protein synthesis: the role of eIF4G

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

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