Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29

Kirn‐Safran, Catherine B.; Oristian, Daniel; Focht, Richard J.; Parker, Shaila G.; Vivian, Jay L.; Carson, Daniel D.

doi:10.1002/dvdy.21046

Cited by 68 publications

(87 citation statements)

References 42 publications

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“…Translation components are drivers of cancer F Loreni et al However, although there is experimental evidence of ribosomes lacking an RP, 135,141,142 the model of ribosome heterogeneity caused by alteration of RP quantity or quality does not seem coherent with the general picture of ribosome biogenesis. In fact, the synthesis of ribosomes is a process that appears to be regulated at multiple levels.…”

Section: Ribosomes and Cancermentioning

confidence: 99%

Translation factors and ribosomal proteins control tumor onset and progression: how?

2013

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Gene expression is shaped by translational control. The modalities and the extent by which translation factors modify gene expression have revealed therapeutic scenarios. For instance, eukaryotic initiation factor (eIF)4E activity is controlled by the signaling cascade of growth factors, and drives tumorigenesis by favoring the translation of specific mRNAs. Highly specific drugs target the activity of eIF4E. Indeed, the antitumor action of mTOR complex 1 (mTORc1) blockers like rapamycin relies on their capability to inhibit eIF4E assembly into functional eIF4F complexes. eIF4E biology, from its inception to recent pharmacological targeting, is proof-of-principle that translational control is druggable. The case for eIF4E is not isolated. The translational machinery is involved in the biology of cancer through many other mechanisms. First, untranslated sequences on mRNAs as well as noncoding RNAs regulate the translational efficiency of mRNAs that are central for tumor progression. Second, other initiation factors like eIF6 show a tumorigenic potential by acting downstream of oncogenic pathways. Third, genetic alterations in components of the translational apparatus underlie an entire class of inherited syndromes known as 'ribosomopathies' that are associated with increased cancer risk. Taken together, data suggest that in spite of their evolutionary conservation and ubiquitous nature, variations in the activity and levels of ribosomal proteins and translation factors generate highly specific effects. Beside, as the structures and biochemical activities of several noncoding RNAs and initiation factors are known, these factors may be amenable to rational pharmacological targeting. The future is to design highly specific drugs targeting the translational apparatus.

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Section: Ribosomes and Cancermentioning

confidence: 99%

Translation factors and ribosomal proteins control tumor onset and progression: how?

2013

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“…Whereas a complete genetic ablation of individual r-proteins leads to severe growth defects and organismal lethality, with only a few known exceptions (Kirn-Safran et al 2007;McIntosh et al 2011;Babiano et al 2012;Steffen et al 2012;O'Leary et al 2013), their suboptimal expression often results in complex pathological phenotypes. In humans, reduced expression or partial loss of function in a number of r-proteins are associated with a group of congenital disorders termed ribosomopathies, characterized by impaired proliferation and increased cell death in hematopoietic progenitors and certain other cell lineages (Ellis and Gleizes 2011;Raiser et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of mature ribosomes by enhancing production of shortened 5.8S rRNA

Wang

Parshin

Shcherbik

et al. 2015

RNA

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Processing of rRNA during ribosome assembly can proceed through alternative pathways but it is unclear whether this could affect the structure of the ribosome. Here, we demonstrate that shortage of a ribosomal protein can change pre-rRNA processing in a way that over time alters ribosome diversity in the cell. Reducing the amount of Rpl17 in mouse cells led to stalled 60S subunit maturation, causing degradation of most of the synthesized precursors. A fraction of pre-60S subunits, however, were able to complete maturation, but with a 5 ′ -truncated 5.8S rRNA, which we named 5.8S C . The 5 ′ exoribonuclease Xrn2 is involved in the generation of both 5.8S C and the canonical long form of 5.8S rRNA. Ribosomes containing 5.8S C rRNA are present in various mouse and human cells and engage in translation. These findings uncover a previously undescribed form of mammalian 5.8S rRNA and demonstrate that perturbations in ribosome assembly can be a source of heterogeneity in mature ribosomes.

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“…Other candidate HS-binding molecules expressed by uterine epithelial cell surfaces include amphiregulin (Das et al 1995) and HIP/RPL29 (Rohde et al 1996). Null mutants have been generated to all of these proteins and none display an overt implantation defect, again probably due to redundancy in function (Luetteke et al 1999;Iwamoto et al 2003;Kirn-Safran, Oristian, et al 2007;Kirn-Safran, Oristian, Focht, et al 2007). It should be noted that all of these proteins may participate in implantation.…”

Section: Perlecan Expression In Embryo Implantation and Placentationmentioning

confidence: 99%

Perlecan a multifunctional extracellular proteoglycan scaffold

2007

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Perlecan is a large multidomain heparan sulfate proteoglycan of the extracellular matrix. Expression of this proteoglycan changes dynamically during embryo implantation and placentation. Perlecan is expressed by various cells of the embryo including trophectoderm and trophoblast as well as the maternal compartment, including basal lamina underlying uterine epithelia and endothelia and, most dynamically, in developing decidua. Perlecan supports various biological functions, including cell adhesion, growth factor binding, and modulation of apoptosis. Moreover, studies in other systems demonstrate that perlecan expression and activity can be controlled at many levels, including transcription, alternative splicing, and extracellular proteolysis. This review will discuss changes in perlecan expression that occur during embryo implantation and placentation. Furthermore, we propose a model in which perlecan represents an extracellular scaffold protein that supports complex, distinct functions in its full-length form or smaller forms generated by alternative mRNA splicing, extracellular proteolysis, or glycosidase action.

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Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29

Cited by 68 publications

References 42 publications

Translation factors and ribosomal proteins control tumor onset and progression: how?

Translation factors and ribosomal proteins control tumor onset and progression: how?

Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of mature ribosomes by enhancing production of shortened 5.8S rRNA

Perlecan a multifunctional extracellular proteoglycan scaffold

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