Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Keeping Growth in Check

Published: Friday, December 13, 2013
Last Updated: Friday, December 13, 2013
Bookmark and Share
Ribosomal proteins RPL5 and RPL11 play an essential role in normal cell proliferation.

Researchers from the Laboratory of Cancer Metabolism (LCM) led by George Thomas at the Bellvitge Biomedical Research Institute (IDIBELL), the Catalan Institute of Oncology (ICO) and the Division of Hematology/ Oncology, University of Cincinnati, have shown that loss of either one of two tumor suppressors, ribosomal proteins RPL5 or RPL11, fail to induce cell-cycle arrest, but prevent the proliferation of cells as they have a reduced capacity to synthesize proteins. Thus, unlike other tumor suppressors, RPL5 and RPL11 play an essential role in normal cell proliferation a function cells have evolved to rely on when their levels are suppressed in lieu of a cell-cycle checkpoint.

The results are “Spotlighted” in the December issue of the journal of Molecular Cellular Biology.

Keeping growth in check

Ribosomes are complex protein/ribonucleic acid macromolecular “machines” composed of approximately eighty distinct RPs and four non-coding ribosomal RNAs (rRNA) which translate the genetic code contained in messenger RNAs (mRNA) into functional proteins. Increased protein synthesis is an essential requirement for cell growth and the subsequent division of a parental cell into two daughter cells. The integrity of both events is tightly monitored to prevent deregulated growth and proliferation typical of a number human pathologies including cancer.

The Thomas team has previously shown that RPL5 and RPL11 together with non-coding 5S RRNA have a mutually dependent extra-ribosomal role as tumor suppressors, through their ability to bind Hdm2. This leads to the stabilization of p53, cell cycle arrest and apoptosis. Wild type cells rely on the tumor suppressor role of RPL5 and RPL11 to activate p53 checkpoint when there is an imbalance between the availability of ribosomal components and the demand for protein synthesis. Thus RPs not only support growth and proliferation, but they have a built-in mechanism through the RPL5/RPL11/5S rRNA-Hdm2 inhibitory checkpoint to prevent unwarranted growth.
Given the importance of RPL5 and RPL11 in tumor suppression, Teng Teng, a PhD. Student in the Thomas Laboratory at the University of Cincinnati set out to investigate the effect of their depletion on global translation, the induction of p53 and cell-cycle progression in primary human cells. They observed the depletion of either RPL5 or RPL11 unlike depletion of other essential RPs of the 60S ribosomal sub unit did not induce p53 but repressed cell proliferation, suggesting that an alternative cell-cycle checkpoint may regulate cell-cycle progression following their reduced expression. However RPL5 and RPl11 depleted cells did not accumulate in any specific phase of cell cycle.

Instead, as shown by BrdU pulse-chase experiments, they progressed at a much slower rate through each phase of the cell-cycle to a similar extent. This effect was associated with the general inhibition of global protein synthesis, such that mRNAs encoding key cyclins, including those of cyclin E1, A2 and B1 were present on polysomes of a smaller mean size in RPL5 and RPl11 depleted cells as compared to control cells. Consistent with this finding, co-depletion of p53 and RPL7a, another essential 60S RP, blocked the induction of the p53 cell-cycle checkpoint, but did not recue cell growth, as the effects of RPL7a depletions on global translation persisted.

The Thomas laboratory findings are consistent with a recent report highlighting the availability of ribosomes as the rate-limiting step in translation initiation. Thus mammalian cells appear to have evolved a general RPL5/RPL11/5SsRNA-dependent cell-cycle checkpoint in response to impaired or hyperactivated ribosome biogenesis, whereas in the case of lesions in RPL5 or RPL11 they rely on their essential role in ribosomes biogenesis, rather than a cell-cycle checkpoint, to limit proliferation.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Key Role of a Protein in the Segregation of Genetic Material During Cell Division
Researchers at IDIBELL have reported an article which delves into the regulator mechanisms of mitosis.
Wednesday, December 11, 2013
Discovered a Mechanism that Induces Migration of Tumor Cells in Liver Cancer
Coordinated overactivation of TGFb and CXCR4 signaling pathways confer migratory properties to the hepatocellular carcinoma cells.
Wednesday, November 06, 2013
Researchers Discover the Genetic Signature of Highly Aggressive Small Lung Tumors
A study conducted by the IDIBELL allows to identify this type of cancer at an early stage and adapt the treatment.
Thursday, October 03, 2013
Discovered Epigenetic Alterations in the Brain of Alzheimer's Patients
Alzheimer disease is becoming a major health problem in Western societies, exacerbated by the progressive aging of the population.
Monday, September 16, 2013
High Levels of RANK Protein Interferes with the Differentiation of Mammary Cells
Levels of this protein increase with age, which could explain the increase in breast cancer risk associated with age.
Wednesday, September 11, 2013
The Epigenome Differentiates the Different Human Populations
Establishing what differentiates us from our neighbors, our friends or strangers from distant countries.
Monday, August 05, 2013
Discovered a Future Therapeutic Target for Lung Cancer Treatment
One of the goals of research in cancer genetics and molecular biology is to get an "on demand" treatment, with maximum effect and minimal toxicity.
Monday, July 22, 2013
Brain Epigenome Changes from Birth to Adolescence
Experience of parents with their children and teachers with their students demonstrate how kids change their behaviours and knowledge from childhood to adolescence.
Friday, July 05, 2013
Discovered the Role of Noncoding 5S rRNA in Protecting the p53 Tumor Suppressor Gene
Over 50% of tumors are associated with mutations in p53.
Thursday, July 04, 2013
A Gene Conserved from Worms to Humans Opens the Door to new Therapeutics
Gene shows promising therapeutic strategies in cancer and in some types of blindness.
Friday, June 21, 2013
An Epigenetic Change Causes the Block of Antitumor Genes
Healthy cells live in a delicate balance between growth-promoting genes (oncogenes) and those who restrain it (anti-oncogenes or tumor suppressor genes).
Wednesday, June 12, 2013
Identified a Key Protein in Maintaining the Identity of B Lymphocytes
This finding could be useful for the study of blood diseases such as lymphoma and leukemia.
Monday, June 10, 2013
Found in Amish a Genetic Mutation Causing Mental Retardation Very Similar to Angelman Syndrome
It is the first time that associates a mutation in HERC2 with human disease.
Wednesday, March 20, 2013
Epigenetic Mechanism through which Protein SirT2 Regulates Cell Cycle Progression and Genomic Stability
The study of IDIBELL researchers confirms antitumor properties of sirtuin 2.
Wednesday, March 20, 2013
Manel Esteller, ''if the Alphabet is Genetics, Spelling is Epigenetics''
Why don’t identical twins have the same disease at the same time? Why do two cats who share the same DNA have different spots? The answer is in epigenetics.
Friday, November 30, 2012
Scientific News
Revolutionary Technologies Developed to Improve Outcomes for Lung Cancer Patients
Breath test to detect lung cancer brings oxygen directly to the wound.
Dementia Linked to Deficient DNA Repair
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer’s disease.
New Gene Map Reveals Cancer’s Achilles’ Heel
Team of researchers switches off almost 18,000 genes
New Discovery Sheds Light on Disease Risk
Gaps between genes interact to influence the risk of acquiring disease.
Mathematical Model Helps Show How Zebrafish Get Their Stripes
The iconic yellow and blue stripes of zebrafish form dynamically as young fish develop and grow. A mathematical model developed by Brown University researchers helps to show how pigment cells interact to form the pattern.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Mathematical Model Forecasts the Path of Breast Cancer
Chances of survival depend on which organs breast cancer tumors colonize first.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos