Loss of a Calcium Requirement for Protein Synthesis in Pituitary Cells following Thermal or Chemical Stress

Brostrom, Margaret A.; Lin, Xiaojin; Cade, Christina; Gmitter, D; Brostrom, Charles O.

doi:10.1016/s0021-9258(18)94234-1

Cited by 20 publications

(7 citation statements)

References 32 publications

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“…Recent experiments suggest that calcium is required for efficient translation in vivo (Brostrom et al, 1989a;Chin et al, 1987). Interestingly, this requirement is lost following thermal or chemical stress (Brostrom et al, 1989b). Others have reported that calcium is required for stability of the 43S preinitiation complex (Kumar et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

The p220 component of eukaryotic initiation factor 4F is a substrate for multiple calcium-dependent enzymes

Wyckoff¹,

Croall²,

Ehrenfeld³

1990

Biochemistry

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Eukaryotic initiation factor 4F (eIF-4F) is a multisubunit protein that functions in the first step of the binding of capped mRNAs to the small ribosomal subunit. Its largest polypeptide component, p220, is cleaved following poliovirus infection. This is thought to inactivate eIF-4F function, thereby preventing cap-dependent initiation of translation of cellular mRNAs. In this report, we show that p220 in extracts of uninfected HeLa cells is specifically lost in the presence of calcium. The responsible activities have been partially purified and identified as the calcium-dependent, neutral, cysteine proteases calpains I and II. In addition, a third calcium-dependent activity was resolved from the calpains and also results in the loss of p220. This activity has properties similar to a transglutaminase and copurifies with tissue transglutaminase through several chromatographic steps. None of these calcium-dependent activities appears to mediate p220 cleavage in poliovirus-infected cells.

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Section: Discussionmentioning

confidence: 99%

The p220 component of eukaryotic initiation factor 4F is a substrate for multiple calcium-dependent enzymes

Wyckoff¹,

Croall²,

Ehrenfeld³

1990

Biochemistry

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“…Yali Xue, 1 * Javier Prado-Martinez, 2 * Peter H. Sudmant, 3 * Vagheesh Narasimhan, 1,4 * Qasim Ayub, 1 Michal Szpak, 1 Peter Frandsen, 5 Yuan Chen, 1 Bryndis Yngvadottir, 1 David N. Cooper, 6 Marc de Manuel, 2 Jessica Hernandez-Rodriguez, 2 Irene Lobon, 2 Hans R. Siegismund, 5 Luca Pagani, 1,7 Michael A. Quail, 1 Christina Hvilsom, 8 Antoine Mudakikwa, 9 Evan E. Eichler, 3,10 Michael R. Cranfield, 11 Tomas Marques-Bonet, 2,12 Chris Tyler-Smith, 1 † Aylwyn Scally 13 † Mountain gorillas are an endangered great ape subspecies and a prominent focus for conservation, yet we know little about their genomic diversity and evolutionary past. We sequenced whole genomes from multiple wild individuals and compared the genomes of all four Gorilla subspecies.…”

Section: Mountain Gorilla Genomes Reveal the Impact Of Long-term Popu...mentioning

confidence: 99%

“…1D and fig. S1), because stress gene expression requires translation recovery (8,9). Activating transcription factor 4 (ATF4) is selectively translated upon stress when eIF2a is phosphorylated (10), and this was SCIENCE sciencemag.org prolonged in Sephin1-treated cells (Fig.…”

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confidence: 99%

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Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit

Das

Krzyżosiak

Schneider

et al. 2015

Science

391

425

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Protein phosphorylation regulates virtually all biological processes. Although protein kinases are popular drug targets, targeting protein phosphatases remains a challenge. Here, we describe Sephin1 (selective inhibitor of a holophosphatase), a small molecule that safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Thus, regulatory subunits of phosphatases are drug targets, a property exploited here to safely prevent two protein misfolding diseases.

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“…The resulting decrease in globin synthesis prevents accumulation of toxic free globin chains and protects developing erythrocytes from destruction under conditions of limited iron availability (Han et al ., 2001). In cells exposed to arsenite or cadmium, eIF2α phosphorylation and translation repression, which are effected by unknown mechanisms, minimize modification of newly synthesized proteins by the reactive transition metal (Brostrom et al ., 1989; Brostrom and Brostrom, 1998). In all three examples, the phosphorylation of eIF2α protects the stressed cell from the toxic potential of its own modified or unfolded proteins.…”

Section: Introductionmentioning

confidence: 99%

Stress-induced gene expression requires programmed recovery from translational repression

Novoa¹,

Zhang²,

Zeng³

et al. 2003

EMBO J

432

427

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Active repression of protein synthesis protects cells against protein malfolding during endoplasmic reticulum stress, nutrient deprivation and oxidative stress. However, long-term adaptation to these conditions requires synthesis of new stress-induced proteins. Phosphorylation of the a-subunit of translation initiation factor 2 (eIF2a) represses translation in diverse stressful conditions. GADD34 is a stress-inducible regulatory subunit of a holophosphatase complex that dephosphorylates eIF2a, and has been hypothesized to play a role in translational recovery. Here, we report that GADD34 expression correlated temporally with eIF2a dephosphorylation late in the stress response. Inactivation of both alleles of GADD34 prevented eIF2a dephosphorylation and blocked the recovery of protein synthesis, normally observed late in the stress response. Furthermore, defective recovery of protein synthesis markedly impaired translation of stressinduced proteins and interfered with programmed activation of stress-induced genes in the GADD34 mutant cells. These observations indicate that GADD34 controls a programmed shift from translational repression to stress-induced gene expression, and reconciles the apparent contradiction between the translational and transcriptional arms of cellular stress responses.

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Loss of a Calcium Requirement for Protein Synthesis in Pituitary Cells following Thermal or Chemical Stress

Cited by 20 publications

References 32 publications

The p220 component of eukaryotic initiation factor 4F is a substrate for multiple calcium-dependent enzymes

The p220 component of eukaryotic initiation factor 4F is a substrate for multiple calcium-dependent enzymes

Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit

Stress-induced gene expression requires programmed recovery from translational repression

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