Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovered the role of noncoding 5S rRNA in protecting the p53 tumor suppressor gene

04.07.2013
Over 50% of tumors are associated with mutations in p53

Researchers of the Cancer Metabolism group at the Bellvitge Biomedical Research Institute (IDIBELL), Catalan Oncology Institute (ICO) and the Division of Hematology-Oncology of the University of Cincinnati, led by George Thomas, have discovered a role for ribosomal 5S RNA in the formation of a complex that regulates the stability of p53.

Normally, p53 prevents healthy cells from becoming tumorigenic. It is maintained at low levels when cells function properly and increases when there is a cellular damage.

The results have been published in the online edition of Cell Reports.

Cell growth

The ability of cells to grow is directly related to the amount of protein synthesized by ribosomes, the intracellular machinery responsible for translating messenger RNA transcribed from DNA into amino acids containing proteins. Misregulation of ribosome biogenesis is associated with extreme forms of aberrant cell growth including anemia and cancer.

Activation of p53 leads to the induction of a cell death program, preventing aberrantly growing cells from initiating tumor development. In normal conditions, p53 is kept at low levels to avoid damaging healthy cells. The chief enzyme that maintains low levels of p53 is Hdm2, which under normal growth conditions degrades p53.

Ribosomes themselves are composed of two subunits termed 40S and 60S. The formation of the 60S involves many molecular constituents, including L5, L11 and 5S rRNA, which form a pre-ribosomal complex before being incorporated into the mature 60S subunit. The Thomas team have shown that when there is damage to ribosomes, or potentially when ribosome biogenesis is hyperactivated, the L5/L11/5S rRNA pre-ribosomal complex is redirected from nascent ribosomes to the binding and inhibition of Hdm2, allowing p53 to rise, leading to cell death.

Recently, the Thomas team showed that L5 and L11 regulate Hdm2 in a mutually dependent manner. Now, Giulio Donati, the first author of these studies, has demonstrated the existence of the L5/L11/5S rRNA pre-ribosomal complex and its role as a tumor suppressor. Strikingly, they also show that the same 5S rRNA species that regulates Hdm2 is also a positive effector of Hdm4, a negative regulator of p53. These findings point to an ancient evolutionary link between ribosome biogenesis and cancer.

Over 50% of tumors

Thomas explained that understanding how p53 is regulated and functions is critical as "more than 50% of tumors have mutations in p53 or overexpress Hdm2 or Hdm4, which blocks the activity of p53". Thomas adds that "we are currently working on the design of a clinical trial, with the Ramon Salazar team (ICO) based on activating Hdm2-p53 checkpoint to kill tumor cells".

Article reference
Donati G., Peddigari S., Mercer C.A. and Thomas G. 5S rRNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint. Cell Reports.

Arantxa Mena | EurekAlert!
Further information:
http://www.idibell.cat

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>