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

July 03, 2013

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".
-end-
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-Bellvitge Biomedical Research Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.