RACK1 Function in Cell Motility and Protein Synthesis

Gandin, Valentina; Senft, Daniela; Topisirović, Ivan; Ronai, Ze’ev A.

doi:10.1177/1947601913486348

Cited by 66 publications

(49 citation statements)

References 78 publications

(118 reference statements)

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“…Asc1 and its mammalian homolog RACK1 are not only part of the small ribosomal subunit but also highly conserved adaptor proteins, which interact with components of various signaling pathways and in this way affect the activity of important kinases (14). It is thus possible that the effect of the ⌬asc1 mutation on ribosomal stalling involves modulation of the activity of ribosomal proteins and/or of translation factors via phosphorylation (2,(89)(90)(91).…”

Section: Discussionmentioning

confidence: 99%

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Chiabudini

Tais

Zhang

et al. 2014

Molecular and Cellular Biology

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bRibosome stalling is an important incident enabling the cellular quality control machinery to detect aberrant mRNA. Saccharomyces cerevisiae Hbs1-Dom34 and Ski7 are homologs of the canonical release factor eRF3-eRF1, which recognize stalled ribosomes, promote ribosome release, and induce the decay of aberrant mRNA. Polyadenylated nonstop mRNA encodes aberrant proteins containing C-terminal polylysine segments which cause ribosome stalling due to electrostatic interaction with the ribosomal exit tunnel. Here we describe a novel mechanism, termed premature translation termination, which releases C-terminally truncated translation products from ribosomes stalled on polylysine segments. Premature termination during polylysine synthesis was abolished when ribosome stalling was prevented due to the absence of the ribosomal protein Asc1. In contrast, premature termination was enhanced, when the general rate of translation elongation was lowered. The unconventional termination event was independent of Hbs1-Dom34 and Ski7, but it was dependent on eRF3. Moreover, premature termination during polylysine synthesis was strongly increased in the absence of the ribosome-bound chaperones ribosome-associated complex (RAC) and Ssb (Ssb1 and Ssb2). On the basis of the data, we suggest a model in which eRF3-eRF1 can catalyze the release of nascent polypeptides even though the ribosomal A-site contains a sense codon when the rate of translation is abnormally low.

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Section: Discussionmentioning

confidence: 99%

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Chiabudini

Tais

Zhang

et al. 2014

Molecular and Cellular Biology

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“…This protein has a seven bladed β-propeller domain that allows it to act as a scaffold, in a manner homologous to the heterotrimeric G protein Gβ subunit. RACK1 is involved in diverse signaling events as well as in translation (Gandin et al, 2013a). Its roles in mammals and yeast include recruitment of the protein kinase C that phosphorylates eIF6 to promote its release from the 60S.…”

Section: Rack1 a Ribosome Interacting Playermentioning

confidence: 99%

Mechanism of Cytoplasmic mRNA Translation

Browning

Bailey‐Serres

2015

The Arabidopsis Book

180

220

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Protein synthesis is a fundamental process in gene expression that depends upon the abundance and accessibility of the mRNA transcript as well as the activity of many protein and RNA-protein complexes. Here we focus on the intricate mechanics of mRNA translation in the cytoplasm of higher plants. This chapter includes an inventory of the plant translational apparatus and a detailed review of the translational processes of initiation, elongation, and termination. The majority of mechanistic studies of cytoplasmic translation have been carried out in yeast and mammalian systems. The factors and mechanisms of translation are for the most part conserved across eukaryotes; however, some distinctions are known to exist in plants. A comprehensive understanding of the complex translational apparatus and its regulation in plants is warranted, as the modulation of protein production is critical to development, environmental plasticity and biomass yield in diverse ecosystems and agricultural settings.

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“…RACK1 plays a critical role in many fundamental cellular processes including cell adhesion, proliferation, migration and protein synthesis through its ability to act as a scaffold within signalling pathways [1][2][3][4]. RACK1 is known to interact with a diverse array of proteins and functions to recruit and shuttle these proteins to their substrates or other binding partners [1,2].…”

Section: Introductionmentioning

confidence: 99%

RACK1 stabilises the activity of PP2A to regulate the transformed phenotype in mammary epithelial cells

Kiely

Adams

Hayes

et al. 2017

Cellular Signalling

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. (2017) RACK1 stabilises the activity of PP2A to regulate the transformed phenotype in mammary epithelial cells. Cellular Signalling, 35, pp. 290-300. (doi:10.1016Signalling, 35, pp. 290-300. (doi:10. /j.cellsig.2016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/128660/ RACK1/PP2A complex is required for cell adhesion, proliferation, migration, invasion.Potential role for the RACK1/PP2A complex in the progression of breast cancer. KeywordsBreast Cancer, RACK1, PP2A, Protein-Protein Interactions. ABSTRACTConflicting reports implicate the scaffolding protein RACK1 in the progression of breast cancer. RACK1 has been identified as a key regulator downstream of growth factor and adhesion signalling and as a direct binding partner of PP2A. Our objective was to further characterise the interaction between PP2A and RACK1 and to advance our understanding of this complex in breast cancer cells. We examined how the PP2A holoenzyme is assembled on the RACK1 scaffold in MCF-7 cells. We used immobilized peptide arrays representing the entire PP2A-catalytic subunit to identify candidate amino acids on the C subunit of PP2A that might be involved in binding of RACK1. We identified the RACK1 interaction sites on PP2A. Stable cell lines expressing PP2A with FR69/70AA, R214A and Y218F substitutions were generated and it was confirmed that the RACK1/PP2A interaction is essential to stabilize PP2A activity. We used Real-Time Cell Analysis and a series of assays to demonstrate that disruption of the RACK1/PP2A complex also reduces the adhesion, proliferation, migration and invasion of breast cancer cells and plays a role in maintenance of the cancer phenotype. This work has significantly advanced our understanding of the RACK1/PP2A complex and suggests a pro-carcinogenic role for the RACK1/PP2A interaction. This work suggests that approaches to target the RACK1/PP2A complex are a viable option to regulate PP2A activity and identifies a novel potential therapeutic target in the treatment of breast cancer.

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RACK1 Function in Cell Motility and Protein Synthesis

Cited by 66 publications

References 78 publications

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Release Factor eRF3 Mediates Premature Translation Termination on Polylysine-Stalled Ribosomes in Saccharomyces cerevisiae

Mechanism of Cytoplasmic mRNA Translation

RACK1 stabilises the activity of PP2A to regulate the transformed phenotype in mammary epithelial cells

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