Transient synthesis of a specific set of proteins during the rapid cleavage phase of sea urchin development

Grainger, James L.; Brunn, Albrecht von; Winkler, Mary G.

doi:10.1016/0012-1606(86)90205-8

Cited by 34 publications

(20 citation statements)

References 39 publications

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“…Thus, SGN-35 has the potential to act on cells within a heterogeneous tumor cell population that do not bind sufficiently high amounts of ADC for effective direct cytotoxic activity. In general, this is of importance because mAbs have been shown to distribute within tumors in an uneven manner and many tumors are heterogeneous with respect to antigen expression (22,39,40). In targeting HL with antibodies directed against CD30 in particular, the ability to eradicate antigen-negative cells within the tumor mass may be useful because only a small percentage of the cells are CD30 positive and thought to be a part of the clonal malignancy (25).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate

Okeley

Miyamoto

Zhang

et al. 2010

Clinical Cancer Research

349

233

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Purpose: SGN-35 is an antibody-drug conjugate (ADC) containing the potent antimitotic drug, monomethylauristatin E (MMAE), linked to the anti-CD30 monoclonal antibody, cAC10. As previously shown, SGN-35 treatment regresses and cures established Hodgkin lymphoma and anaplastic large cell lymphoma xenografts. Recently, the ADC has been shown to possess pronounced activity in clinical trials. Here, we investigate the molecular basis for the activities of SGN-35 by determining the extent of targeted intracellular drug release and retention, and bystander activities.Experimental

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Section: Discussionmentioning

confidence: 99%

Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate

Okeley

Miyamoto

Zhang

et al. 2010

Clinical Cancer Research

349

233

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“…Protein synthesis is required for cell division to occur (15,32,33). It appears likely that a large proportion of the proteins synthesized after fertilization are required for the cell cycle (11,13).The increase in the rate of protein synthesis appears to be mediated by both the availability of translationally competent mRNAs and an increase in the activity of components of the translational machinery (34). Modulation of the activity * Corresponding author.…”

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confidence: 99%

Fertilization triggers unmasking of maternal mRNAs in sea urchin eggs.

Grainger¹,

Winkler²

1987

Mol. Cell. Biol.

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Fertilization of sea urchin eggs results in a large increase in the rate of protein synthesis which is mediated by the translation of stored maternal mRNA. The masked message hypothesis suggests that messenger ribonucleoprotein particles (mRNPs) from unfertilized eggs are translationally inactive and that fertilization results in alterations of the mRNPs such that they become translationaHy active. Previous workers have isolated egg mRNPs by sucrose gradient centrifugation and have assayed their translational activity in heterologous cell-free systems. The conflicting results they obtained are probably due to the sensitivity of mRNPs to artifactual activation and inactivation. Previously, we demonstrated that unfractionated mRNPs in a sea urchin cell-free translation system were translationally inactive. Now, using large-pore gel filtration chromatography, we partially purified egg mRNPs while retaining their translationally repressed state. Polysomal mRNPs from fertilized eggs isolated under the same conditions were translationally active. The changes in the pattern of proteins synthesized by fractionated unfertilized and fertilized mRNPs in vitro were similar to those changes observed in vivo. Treatment of egg mRNPs with buffers containing high salt and EDTA, followed by rechromatography, resulted in the activation of the mRNPs and the release of an inhibitor of translation from the mRNPs. Analysis of the inhibitory fraction on one-dimensional sodium dodecyl sulfate gels indicated that this fraction contains a complex set of proteins, several of which were released from high-salt-EDTA-activated mRNPs and not from inactive low-salt control mRNPs. One of the released proteins may be responsible for the repression of egg mRNPs in vitro and be involved in the unmasking of mRNPs at fertilization.One of the major changes that occurs upon activation of a variety of cell types is an increase in the overall rate of protein synthesis. This increase is largely mediated by the regulation, at the translational level, of mRNAs stored in these quiescent cells. Examples of this type of translational control include the serum stimulation of resting fibroblasts, fertilization of various invertebrate and vertebrate oocytes, and the activation of T lymphocytes (30; for reviews, see references 18 and 26).It appears that many of the basic mechanisms that control the activation of protein synthesis in these various cell types occur in an amplified or exaggerated form after fertilization of sea urchin eggs. The increase in intracellular calcium and pH that follows fertilization results in the mobilization of maternal mRNAs into polysomes (10,14,36). These mRNAs were synthesized during oogenesis and stored in the unfertilized egg as messenger ribonucleoprotein particles (mRNPs). The specific regulatory pathways by which changes in intracellular ion concentrations result in the mobilization of these mRNPs into polysomes are not yet known.The increase in the rate of protein synthesis after fertilization is mainly due to an increase in t...

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“…Chez le Marsilea, l'emhryogenese precoce pourrait etre, comme cela a ete note chez de nomhreuses especes animales (Grainger et al, 1986 ;Taylor et al, 1986;Schauer et Wood, 1990;Jarrei et al, 1991) sous la dependance de deux populations de molecules proteiques. La premiere serait vraisemhlablement synthetisee pendant l'oogenese dans le gamete femelle puis stockee, Ia seconde serait neosynthetisee au cours des 3 premiers cycles cellulaires a partir d'ARNm, r et t transcrits pendant l'oogenese, accumules dans le zygote et actives apres la fecondation.…”

Section: Introductionunclassified

“…'edification des premiers blastomeres, proteines de type structural de ! 'edification du fuseau (actine, tubuline) ou enzymatique permettant Ia synthese de l'ADN (polymerases), seraient des proteines elaborees au cours de Ia gametogenese femelle puis stockees dans l'oosphere mature (Grainger et al, 1986) ou eventuellement des proteines nouvellement synthetisees, mais dont ! 'elaboration n'est pas inhibee par le froid.…”

Section: Introductionunclassified

Evolution des activités transcriptionnelle et traductionnelle au cours de l'embryogenèse duMarsilea vestita

Chenou¹,

Kuligowski²,

Ferrand³

1994

Acta Botanica Gallica

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Summary.-A weak cooling (24°C ~ 16°C) applied during Marsi/ea vestita embryogenesis induces a decrease in the transcriptional and proteogenesis activities linked to morphological. structural and ultrastructural changes. The obtained results strongly suggest that embryogenesis is under the control of at least three different populations of proteins. The first one, little sensitive to the cooling, synthesized during gametogenesis and stored in the egg may be useful to the mitotic spindle edification and the DNA synthesis. The second, more sensitive to the cooling, translated from pre-existing RNA stored in the egg, probably consists in factors responsible for the rapidity and the synchrony of the cleavages. The last one is dependent on the translation both of newly synthesized RNA of embryonic origin and mANA brought by the spermatozoid. This spermatic mANA could play a role in further cellular differenciation.Key words : fern embryo • stored mANA • proteins • paternal mANA -temperature effect.©Societe botanique de France 1994

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Transient synthesis of a specific set of proteins during the rapid cleavage phase of sea urchin development

Cited by 34 publications

References 39 publications

Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate

Intracellular Activation of SGN-35, a Potent Anti-CD30 Antibody-Drug Conjugate

Fertilization triggers unmasking of maternal mRNAs in sea urchin eggs.

Evolution des activités transcriptionnelle et traductionnelle au cours de l'embryogenèse duMarsilea vestita

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