The Dynamic Role of GRP78/BiP in the Coordination of mRNA Translation with Protein Processing

Laitusis, Algis L.; Brostrom, Margaret A.; Brostrom, Charles O.

doi:10.1074/jbc.274.1.486

Cited by 83 publications

(87 citation statements)

References 37 publications

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“…In this case, there are additionallonger term adaptive responses to calcium changes, which can also be correlated with the regulation of eIF2a phosphorylation. Calcium mobilisation leads to transcriptional induction of genes co ding for proteins such as Grp78/BiP, an ERassociated molecule which co-ordinates translation with protein processing and facilitates the subsequent tolerance of protein synthesis to the original inhibitory stress Laitusis et al 1999). Grp78 induction itself is independent of eIF2a phosphorylation but the subsequent adjustment of the initiation rate is associated with a decrease in the phosphorylation of eIF2a (Prostko et al 1992).…”

Section: Regulation By Calciummentioning

confidence: 97%

Initiation Factor eIF2α Phosphorylation in Stress Responses and Apoptosis

Clemens

2001

Progress in Molecular and Subcellular Biology

205

146

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Protein synthesis in eukaryotes is a complex process which can be regulated at many points in the pathway. In re cent years it has become dear that both the overall rate of translation and the relative rates of synthesis of individual proteins can be controlled post-transcriptionally through changes in the activities or levels of a small number of key components, and that such regulation usually takes pi ace at the level of polypeptide chain initiation. A large body of evidence indicates that the essential polypeptide chain initiation factor eIF2 is a frequent target for regulation, and that its activity is often rate-limiting for protein synthesis. The phosphorylation of the smallest (a) subunit of eIF2 is a widely used mechanism of translational control in many organisms, and there are numerous physiologically important situations where eIF2a kinases are activated or inhibited. This chapter provides a review of our knowledge concerning the mechanisms by which eIF2 is controlled by reversible pro tein phosphorylation.A great variety of intracellular and extraceHular influences can alter rates of protein synthesis. One important dass of such influences can be grouped under the general heading of ceHular stresses. In the broadest sense, these range from normal physiological changes such as variations in nutrient availability or the actions of growth factors and cytokines to pathological conditions such as virus infection, hyperthermia or the presence of toxic compounds. In some cases, these conditions can result in cell death by apoptosis. Modulation of eIF2a phosphorylation is often involved in these situations. The present state of knowledge of how this is brought about and what the physiological consequences may be for the activities of the ceH, induding its survival or death, are reviewed here.Limitations of space predude a detailed account of the mechanism of polypeptide chain initiation and the reader is referred to recent comprehensive reviews (Pain 1996; Kozak 1999;Preiss and Hentze 1999) for such information. Briefly, initiation factor eIF2 catalyses the binding of the initiator

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Section: Regulation By Calciummentioning

confidence: 97%

Initiation Factor eIF2α Phosphorylation in Stress Responses and Apoptosis

Clemens

2001

Progress in Molecular and Subcellular Biology

205

146

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“…Instead, our immunofluorescence images showed variations in the intensity of fluorescence with each antiserum, as reflected in both the images and the laser settings used to generate the images. NFProx antiserum, which recognizes both pro-SP-B and the excised N terminus by Western blotting, colocalized predominantly with the lumenal endoplasmic reticulum marker BiP (29,30). This places pro-SP-B predominantly in the endoplasmic reticulum, which is in agreement with previous work by Voorhout and colleagues (9).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Localization of Processing Events in Human Surfactant Protein B Biosynthesis

Korimilli

Gonzales

Guttentag

2000

Journal of Biological Chemistry

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Surfactant protein B (SP-BThe 8-kDa protein is the result of extensive post-translational processing of a large 381-amino acid precursor within alveolar type 2 cells. Previous studies in cell lines, isolated rat type 2 cells, and human fetal lung (2-7) indicated that processing to the mature 8-kDa protein involves signal peptide cleavage and glycosylation of the C terminus, followed by cleavage of the N terminus and C terminus in succession. We have recently shown that cleavage of the N terminus occurs in two steps, leaving an approximately 10-amino acid remnant flanking mature SP-B which is removed in a final processing step that releases mature SP-B (8). The subcellular location of these processing events and the enzymes necessary for processing SP-B are poorly understood. Previous work by Voorhout and colleagues (9) utilizing immunoelectron microscopy with antisera to mature SP-B and a synthetic pro-SP-B showed pro-SP-B in the endoplasmic reticulum and mature SP-B in lamellar bodies of adult human type 2 cells. Analysis of grain density over other organelles showed intermediate grain densities over multivesicular bodies and Golgi, indicating the involvement of these organelles in SP-B transport and/or processing.The extensive post-translational processing of SP-B is similar to the post-translational processing of the other hydrophobic surfactant protein, SP-C (10 -13). The 21-kDa pro-SP-C undergoes sequential enzymatic cleavages resulting in a 3.7-kDa mature protein. Pro-SP-C is detected in endoplasmic reticulum and a 6-kDa intermediate is enriched in lamellar bodies. Inhibitors of intracellular trafficking and acidification in vitro disrupt all processing beyond the 16-kDa SP-C intermediate. Processing of SP-B and SP-C are linked, since in alveolar type 2 cells of patients with inherited SP-B deficiency SP-C is not processed beyond the 6-kDa intermediate (14,15).In this report, we use epitope-specific antisera and pulsechase labeling studies with inhibitors of protein processing to show that most human pro-SP-B processing is in post-endoplasmic reticulum but pre-lamellar body compartments. Our data extend previous observations of pro-SP-B trafficking and processing to show that early N-terminal propeptide and Cterminal propeptide processing events occur within the Golgi apparatus with processing of the small vestigial N-terminal propeptide domain as a post-Golgi event. We speculate that the N-terminal remnant is involved in trafficking SP-B toward the lamellar body. Previous reports of these data have appeared elsewhere in abstract form (16,17).

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“…Intracellular mono-ADP-ribosylation in mammals modifies proteins that have important roles in cell signaling and metabolism, including, among those best characterized, the chaperone GRP78/BiP, the ␤ subunit of G proteins, and GDH (16)(17)(18)(19)29).…”

Section: Purification and Identification Of Substrates Of Intracellulmentioning

confidence: 99%

Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteome

Dani

Stilla

Marchegiani

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

104

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Mono-ADP-ribosylation is a reversible posttranslational modification that modulates the function of target proteins. The enzymes that catalyze this reaction in mammalian cells are either bacterial pathogenic toxins or endogenous cellular ADP-ribosyltransferases. For the latter, both the enzymes and their targets have largely remained elusive, mainly due to the lack of specific techniques to study this reaction. The recent discovery of the macro domain, a protein module that interacts selectively with ADP-ribose, prompted us to investigate whether this interaction can be extended to the identification of ADP-ribosylated proteins. Here, we report that macro domains can indeed be used as selective baits for high-affinity purification of mono-ADP-ribosylated proteins, which can then be identified by mass spectrometry. Using this approach, we have identified a series of cellular targets of ADP-ribosylation reactions catalyzed by cellular ADP-ribosyltransferases and toxins. These proteins include most of the known targets of ADP-ribosylation, indicating the validity of this method, and a large number of other proteins, which now need to be individually validated. This represents an important step toward the discovery of new ADP-ribosyltransferase targets and an understanding of the physiological role and the pharmacological potential of this protein modification.ADP-ribosylation ͉ ADP-ribosyltransferase ͉ NAD ͉ toxin ͉ posttranslational modification

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The Dynamic Role of GRP78/BiP in the Coordination of mRNA Translation with Protein Processing

Cited by 83 publications

References 37 publications

Initiation Factor eIF2α Phosphorylation in Stress Responses and Apoptosis

Initiation Factor eIF2α Phosphorylation in Stress Responses and Apoptosis

Intracellular Localization of Processing Events in Human Surfactant Protein B Biosynthesis

Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteome

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