Found a mechanism of cell protection against cancer

15 07 2013

Discover the role of the non-coding RNA, 5S rRNA in the protection of the p53 tumor suppressor gene

More than the 50% tumors are related to mutations in this gene

 

Los investigadores George Thomas i Giulio Donati

The researchers George Thomas i Giulio Donati

 

Researchers from the Group of metabolism and Cancer of the Institute of biomedical research of Bellvitge (IDIBELL), of the Catalan Institute of Oncology (ICO) and of the University of Cincinnati, led by George Thomas, they have discovered the role of RNA ribosomal 5S in the formation of a complex that regulates p53 stability. Normally, p53 prevents healthy cells to become tumor. Maintaining low and stable levels when the cell working properly and makes them increase when there is damage in the cell.

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

 

Cell growth

Cell growth is related to the amount of proteins that synthesize the cell Ribosomes, an intracellular machinery responsible for translating messenger RNA molecules, from DNA, in chains of amino acids, forming proteins). The malfunction in the formation of Ribosomes is related to disorders associated with aberrant as anemia and cancer cell growth

Activation of p53 induces the activation of a program of cell death that prevents cells that grow in aberrant way to develop a tumor. Under normal conditions, stays at low levels to avoid damaging healthy cells. The major protein in the maintenance of low levels of p53 is Hdm2, in normal cell growth conditions, degrades p53.

Ribosomes are composed of two subunits called 40S and 60S. In the formation of the subunit 60S involved different molecules, including L5, L11 and 5S rRNA, forming a pre-ribosomal complex before being incorporated into the 60S subunit. The laboratory of George Thomas has shown that when there is damage in the Ribosomes, or when the formation of Ribosomes is hiperactivada the pre-ribosomal complex l5/L11/5S rRNA deviates from its path to form Ribosomes and joins Hdm2 blocking its activity, allowing to increase the levels of p53 and induction of cell death.

Previously, the team of George Thomas had already proved that L5 and L11 regulates Hdm2. Have now discovered the existence of East pre-ribosomal complex formed by L5, L11 and also 5S rRNA and their role as suppressor of tumors. These results point to an ancient evolutionary link between biogenesis of Ribosomes and cancer

 

More than the 50% tumors

George Thomas has explained to understand how it works and how it regulates p53 is important because “more than the 50% tumors have mutations in p53 or overexpress Hdm2 or Hdm4, it blocks the activity of p53″. Thomas adds that “We are currently working on the design of a clinical trial, in colabroracion with the team of Ramon Salazar, based on activating the Hdm2-p53 control point to attack tumor cells".

 

 

The 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

 

 

idibell.cat [en línea] Barcelona (ESP): idibell.cat, 15 de julio de 2013 [REF. 03 in July of 2013] Available on Internet:http://www.idibell.cat/modul/noticias/es/586/descubren-el-papel-del-rna-no-codificante-5s-rrna-en-la-proteccion-del-gen-supresor-de-tumores-p53


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