Physiological effects of translation initiation factor IF3 and ribosomal protein L20 limitation in

1996 ◽  
Vol 250 (6) ◽  
pp. 705 ◽  
Author(s):  
C. L. Olsson ◽  
Monique Graffe ◽  
Mathias Springer ◽  
John W. B. Hershey
Keyword(s):  
Ribosomal Protein ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Physiological Effects

scholarly journals Molecular mechanisms relating to amino acid regulation of protein synthesis

2019 ◽  
Vol 32 (2) ◽  
pp. 183-191 ◽  
Author(s):  
Yangchun Cao ◽  
Shimin Liu ◽  
Kai Liu ◽  
Imtiaz Hussain Raja Abbasi ◽  
Chuanjiang Cai ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Translation Initiation ◽  
Molecular Mechanisms ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Signalling Pathways ◽  
Control Of Gene Expression ◽  
Ribosomal Protein S6 ◽  
New Findings

AbstractSome amino acids (AA) act through several signalling pathways and mechanisms to mediate the control of gene expression at the translation level, and the regulation occurs, specifically, on the initiation and the signalling pathways for translation. The translation of mRNA to protein synthesis proceeds through the steps of initiation and elongation, and AA act as important feed-forward activators that are involved in many pathways, such as the sensing and the transportation of AA by cells, in these steps in many tissues of mammals. For the translation, phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) is a critical molecule that controls the translation initiation and its functions can be regulated by some AA. Another control point in the mRNA binding step in the translation initiation is at the regulation by mammalian target of rapamycin, which requires a change of phosphorylation status of ribosomal protein S6. In fact, the change of phosphorylation status of ribosomal protein S6 might be involved in global protein synthesis. The present review summarises recent work on the molecular mechanisms of the regulation of protein synthesis by AA and highlights new findings.

scholarly journals Down-Regulation of RpS21, a Putative Translation Initiation Factor Interacting with P40, Produces Viable Minute Imagos and Larval Lethality with Overgrown Hematopoietic Organs and Imaginal Discs

1999 ◽  
Vol 19 (3) ◽  
pp. 2308-2321 ◽  
Author(s):  
István Török ◽  
Daniela Herrmann-Horle ◽  
István Kiss ◽  
Gabriela Tick ◽  
Gábor Speer ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Translation Initiation ◽  
Imaginal Discs ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Down Regulation ◽  
Genetic Studies ◽  
Ribosomal Subunits ◽  
Peripheral Protein ◽  
Hematopoietic Organs

ABSTRACT Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minutephenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista(sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth inrpS21-deficient larvae, whereas viable combinations betweenrpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.

Constitutive Activation of FRAP/mTOR Pathway in Pediatric Anaplastic Large Cell Lymphomas: Potential Role as a Therapeutic Target.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 290-290 ◽  
Author(s):  
Megan S. Lim ◽  
Charles Seiler ◽  
Sheryl Tripp ◽  
Sherrie L. Perkins ◽  
Mitchell S. Cairo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Western Blot ◽  
Ribosomal Protein ◽  
Translation Initiation ◽  
Large Cell ◽  
Mtor Pathway ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Alk Positive

Abstract Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p23;q35) is a key oncogenic event in the majority of pediatric anaplastic large cell lymphomas (ALCL). To determine the pathogenetic mechanisms involved in NPM/ALK-mediated lymphomagenesis we employed a mass spectrometry (MS)-based proteomics approach to identify changes in protein expression caused by the overexpression of NPM/ALK. We identified many proteins which were downstream targets of the FRAP/mTOR pathway including ribosomal S6 kinase (1.6-fold), translational initiation factor eIF (4.8-fold), ribosomal protein L11 (4.8-fold), eukaryotic translation initiation factor 3 (3.2-fold), translation initiation factor IF-2 homolog (4.3-fold) and translation initiation factor eIF-2alpha kinase (3.4-fold). The FRAP/mTOR pathway plays a key role in the regulation of cell growth and proliferation and positively regulates translation and ribosome biogenesis and is selectively inhibited by rapamycin. To determine the feasibility of targeting the FRAP/mTOR pathway by rapamycin for treatment of pediatric ALCLs, we determined the prevalence of expression of key proteins in the FRAP/mTOR pathway in pediatric ALCLs and correlated its expression with that of the ALK protein. In addition we determined the in vitro effect of rapamycin on the viability of cell lines derived from t(2;5)-positive ALCLs. We used formalin-fixed paraffin-embedded tissues of ALK-positive ALCLs (n=18) obtained from the Children’s Oncology Group clinical trials (CCG5941 and ANHL0131) and determined the expression of phospho-mTOR, phospho-70S6Kinase and phospho-S6 ribosomal protein using immunohistochemistry. The effect of rapamycin on the viability of cell lines derived from t(2;5)-positive ALCLs was determined by MTT assay and cell cycle analysis. Western blot analysis was performed to determine the effect of rapamycin on cell cycle proteins and apoptosis. Immunohistochemical studies demonstrated diffuse strong nuclear expression of phospho-mTOR in 17/18 cases, and nuclear and cytoplasmic phospho-70S6kinase expression in 15/18 cases. In addition, cytoplasmic expression of phospho-S6 ribosomal protein was observed in 18/18 (100%) of cases. Importantly, the reactive lymphocytes demonstrated negligible expression of all three proteins. Furthermore, rapamycin potently decreased the viability of SUDHL-1 cells (30% reduction by 10nM at 48 hours) and resulted in G1 cell cycle arrest without induction of caspase-3 activity. Western blot analysis demonstrated a reduction in the level of phospho-p70S6Kinase as well as 4EBP-1 levels. Our studies demonstrate overexpression of many proteins in the FRAP/mTOR pathway in NPM/ALK-positive ALCLs. Our data indicate that the majority of pediatric ALCLs express proteins in the FRAP/mTOR pathway and are constitutively activated. Furthermore, our in vitro data support the use of rapamycin as a therapeutic agent in ALK-positive ALCLs.

Sign in / Sign up

Export Citation Format

Share Document