PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Tumor suppressor forms gel-like assemblies to sacrifice cancer cells

Tumor suppressor forms gel-like assemblies to sacrifice cancer cells
2024-11-11
(Press-News.org)

(MEMPHIS, Tenn. – November 11, 2024) There are processes in the human body that can suppress the growth and proliferation of cancer cells. These mechanisms, including those involving the tumor suppressor protein p53, are widely studied due to their critical role in disease. Through studies of proteins that regulate p53, scientists at St. Jude Children’s Research Hospital have uncoupled a previously unrecognized tumor suppression mechanism. Usually found at low levels in cells, the p14 Alternative Reading Frame protein (p14ARF) is expressed at higher levels under oncogenic stress and activates p53. The researchers identified an alternative tumor suppression mechanism for p14ARF, showing how condensate formation and ribosome production disruption contribute to the process. The findings were published today in Nature Communications.

 

The researchers demonstrated that increased expression of p14ARF causes the protein to phase separate with other cellular components. This occurs within the nucleolus, a membraneless compartment in the nucleus of cells responsible for ribosome production. In the nucleolus, p14ARF binds to and phase separates with nucleophosmin, an essential protein for ribosome production, creating a gel-like state, leading to decreased nucleophosmin dynamics, stalled ribosome biogenesis and cell toxicity. The process, kickstarted by p14ARF, thus represents a likely alternative tumor suppressive pathway.

 

p14ARF gums up the works in the nucleolus

 

“p14ARF is normally expressed at very low levels in healthy cells, but increased expression is induced in response to oncogenic stress, such as upregulation of MYC or other oncogenes,” explains corresponding author Richard Kriwacki, PhD, St. Jude Department of Structural Biology.

 

Kriwacki’s investigations into p14ARF function began when the protein, upon increased expression, was found to localize to the nucleolus. Through interaction with nucleophosmin, a protein abundant within the nucleolus that acts as director of the ribosome factory, p14ARF becomes a spanner in the works of the nucleolus, disrupting its normal function. 

 

“Upon overexpression, p14ARF can go to the nucleolus and block nucleophosmin from acting as a chaperone and shuttling pre-ribosomal particles out,” explained first author Eric Gibbs, Department of Structural Biology. “So, nucleophosmin gets stuck in the nucleolus, and consequently, the ribosomal particles get stuck.”

 

Gibbs and Kriwacki showed previously that, in isolation, p14ARF and nucleophosmin form biomolecular condensates. The formation of condensates, which often appear as droplets under a microscope, has been shown to regulate an increasingly abundant number of biological processes, ranging from transcription to cell signaling. Generally, condensates do this by temporarily increasing the localized concentration of specific biomolecules such as DNA, RNA and proteins. However, biomolecules need a sequence-specific “ticket to ride” to participate in phase separation. 

 

p14ARF networking is key to tumor suppression

 

Gibbs and Kriwacki leveraged biophysical techniques, including small-angle neutron scattering (performed at Oak Ridge National Laboratory) and nuclear magnetic resonance spectroscopy, to explore the peculiar nature of p14ARF-nucleophosmin condensates. “We found that p14ARF was not only phase separating with nucleophosmin but also assembling a large network structure that had some symmetry,” explained Gibbs. “This network was responsible for restricting the dynamics of p14ARF and nucleophosmin inside the condensates.” 

 

Furthermore, while p14ARF is generally considered an intrinsically disordered protein lacking stable structure, the researchers noticed that it showed elements of secondary structure within the condensates, which facilitate the formation of the network. “We found that hydrophobic interfaces in the secondary structure regions form the different crosslinks to assemble the network and essentially give the condensate its unique characteristics,” explained Gibbs. The ordered nature of the network led to the condensates taking on a gel-like state, effectively locking nucleophosmin in place.

 

The findings illuminate a previously unknown route by which p14ARF contributes to tumor suppression. Additionally, since condensates usually rely on fluid dynamics to achieve their function, with solidification often associated with a disease-causing state, this work provides a unique perspective on biomolecular condensation. 

 

“I think it’s fascinating that an aspect of how p14ARF acts as a tumor suppressor is through immobilization of the liquid-like nucleolus and apparent inhibition of critical steps in ribosome biogenesis,” explained Kriwacki. “We can now view how p14ARF acts as a tumor suppressor through the lens of what we normally view as a deleterious effect within the nucleolus.”

 

Authors and funding

 

The study’s other authors are Aila Hassan, Rainer Kümmerle, and Barbara Perrone; Bruker Switzerland AG; Gergely Nagy, Wellington Leite, William Heller and Chris Stanley; Oak Ridge National Laboratory; and Qi Miao, Mylene Ferrolino, Richa Bajpai, Aaron Phillips, Aaron Pitre and Shondra Miller; St. Jude.

 

The study was supported by grants from the National Institute of General Medical Sciences (5R35GM131891, 1F32GM133078) and ALSAC, the fundraising and awareness organization of St. Jude.

 

St. Jude Media Relations Contacts

Chelsea Bryant 
Desk: (901) 595-0564
Cell: (256) 244-2048
chelsea.bryant@stjude.org
media@stjude.org

 

Rae Lyn Hartley
Desk: (901) 595-4419
Cell: (901) 686-2597

raelyn.hartley@stjude.org

media@stjude.org

 

St. Jude Children’s Research Hospital 

St. Jude Children’s Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read Progress: A Digital Magazine and follow St. Jude on social media at @stjuderesearch.  

END


[Attachments] See images for this press release:
Tumor suppressor forms gel-like assemblies to sacrifice cancer cells Tumor suppressor forms gel-like assemblies to sacrifice cancer cells 2 Tumor suppressor forms gel-like assemblies to sacrifice cancer cells 3

ELSE PRESS RELEASES FROM THIS DATE:

New research uncovers how Barred Owls interact with urban areas and why it matters

New research uncovers how Barred Owls interact with urban areas and why it matters
2024-11-11
Baton Rouge, November 4, 2024 – Novel research just published in the American Ornithological Society journal, Ornithological Applications, has revealed noteworthy insights into how Barred Owls (Strix varia) interact with urban environments, with implications for both wildlife conservation and urban planning. This study, conducted by a team of biologists from Louisiana State University and other institutions, highlights the connection between owl habitat selection and an urban landscape, underscoring the ...

50 years of survey data confirm African elephant decline

50 years of survey data confirm African elephant decline
2024-11-11
Habitat loss and poaching have driven dramatic declines in African elephants, but it is challenging to measure their numbers and monitor changes across the entire continent. A new study has analyzed 53 years of population survey data and found large-scale declines in most populations of both species of African elephants.  From 1964-2016, forest elephant populations decreased on average by 90%, and savanna elephant populations fell on average by 70%. In combination, populations declined by 77% on average. The study compiled survey data from 475 sites in 37 countries, making it the most comprehensive assessment of African elephants to date.  Declines ...

Swirling polar vortices likely exist on the Sun, new research finds

Swirling polar vortices likely exist on the Sun, new research finds
2024-11-11
EMBARGOED: Until 3 p.m. ET on Monday, Nov. 11, 2024 Contacts:  Laura Snider, NSF NCAR and UCAR Manager of Science Communications lsnider@ucar.edu  303-827-1502 David Hosansky, NSF NCAR and UCAR Manager of Media Relations hosansky@ucar.edu  720-470-2073 Like the Earth, the Sun likely has swirling polar vortices, according to new research led by the U.S. National Science Foundation National Center for Atmospheric Research (NSF NCAR). But unlike on Earth, the formation and evolution of these vortices ...

Protein degradation strategy offers new hope in cancer therapy

Protein degradation strategy offers new hope in cancer therapy
2024-11-11
RIVERSIDE, Calif. -- In drug discovery, targeted protein degradation is a method that selectively eliminates disease-causing proteins. A University of California, Riverside team of scientists has used a novel approach to identify protein degraders that target Pin1, a protein involved in pancreatic cancer development.  The team reports today in the Proceedings of the National Academy of Sciences that it has designed agents that not only bind tightly to Pin1 but are designed to cause its destabilization and cellular ...

Mental fatigue leads to loss of self-control by putting brain areas to sleep

2024-11-11
Prolonged mental fatigue can wear down brain areas crucial for the individual ability to self-control, and cause people to behave more aggressively.  In a new multidisciplinary study published in the PNAS, a group of researchers from neuroscience and economics at the IMT School of Advanced Studies Lucca links the debated concept of "ego depletion", that is to say the diminution of willpower caused by previous exploitation of it, to physical changes in the areas that govern executive functions in the brain. In particular, the ...

Was ‘Snowball Earth’ a global event? New study delivers best proof yet

Was ‘Snowball Earth’ a global event? New study delivers best proof yet
2024-11-11
Geologists have uncovered strong evidence from Colorado that massive glaciers covered Earth down to the equator hundreds of millions of years ago, transforming the planet into an icicle floating in space.  The study, led by the University of Colorado Boulder, is a coup for proponents of a long-standing theory known as Snowball Earth. It posits that from about 720 to 635 million years ago, and for reasons that are still unclear, a runaway chain of events radically altered the planet’s climate. Temperatures plummeted, and ice sheets that may have been several miles thick crept over every inch of Earth’s surface. “This study presents the first physical evidence ...

Scientists issue call to action underlining importance of microbial solutions to tackle climate crisis

2024-11-11
Ahead of COP29, Applied Microbiology International (AMI) has partnered with leading global scientific organisations to issue a unified call to action, spotlighting microbial solutions as pivotal in combating climate change. In a strategic publication, released in multiple high-impact scientific journals at once, the joint paper advocates for the establishment of a global science-driven climate task force.  This initiative aims to expedite the deployment of microbiome technologies, providing stakeholders worldwide with access to effective and immediate solutions. Signatories of the paper, ‘Microbial solutions must be deployed against the climate catastrophe’ ...

Ochsner Transplant Institute among site collaborators in New England Journal of Medicine HIV-to-HIV kidney transplant study

2024-11-11
NEW ORLEANS – The Ochsner Transplant Institute served as one of 26 U.S. transplant centers collaborating in an HIV-to-HIV kidney transplant study published by The New England Journal of Medicine (NEJM). The article, Safety of Kidney Transplantation from Donors with HIV, details findings supporting HIV-to-HIV kidney transplants as safe and just as effective as those using organs from donors without HIV.  Human immunodeficiency virus, commonly known as HIV, attacks cells in the body that fight infection and there is currently no known cure. In the U.S.,1.2 million people are living with HIV. According to the National ...

Scientists call for global action on microbial climate solutions

2024-11-11
Washington, D.C. — Nov. 11, 2024 — Today, leaders from scientific societies, institutions and publishing bodies issued an urgent call for the global community and governments to take immediate and decisive emergency climate action. This appeal is made through an editorial published in mSystems, released on the opening day of the 2024 United Nations Climate Change Conference (COP29). Key contributors to this initiative include Virginia Miller, past president of the American Society for Microbiology (ASM); Jack Gilbert, Editor-in-Chief of mSystems; and Jay Lennon, ...

New antibody could be promising cancer treatment

New antibody could be promising cancer treatment
2024-11-11
Researchers at Uppsala University and KTH Royal Institute of Technology have developed a new form of precision medicine, an antibody, with the potential to treat several types of cancer. Researchers have managed to combine three different functions in the antibody, which together strongly amplify the effect of T cells on the cancer tumour. The study has been published in Nature Communications. Researchers have developed a unique type of antibody that both targets and delivers a drug package via the antibody itself, while simultaneously activating the immune system (“3-in-1 design”) for personalised immunotherapy treatments. “We ...

LAST 30 PRESS RELEASES:

Scientists find a region of the mouse gut tightly regulated by the immune system

How school eligibility influences the spread of infectious diseases: Insights for future outbreaks

UM School of Medicine researchers link snoring to behavioral problems in adolescents without declines in cognition

The Parasaurolophus’ pipes: Modeling the dinosaur’s crest to study its sound #ASA187

St. Jude appoints leading scientist to create groundbreaking Center of Excellence for Structural Cell Biology

Hear this! Transforming health care with speech-to-text technology #ASA187

Exploring the impact of offshore wind on whale deaths #ASA187

Mass General Brigham and BIDMC researchers unveil an AI protein engineer capable of making proteins ‘better, faster, stronger’

Metabolic and bariatric surgery safe and effective for patients with severe obesity

Smarter city planning: MSU researchers use brain activity to predict visits to urban areas

Using the world’s fastest exascale computer, ACM Gordon Bell Prize-winning team presents record-breaking algorithm to advance understanding of chemistry and biology

Jeffrey Hubbell joins NYU Tandon to lead new university-wide health engineering initiative & expand the school’s bioengineering focus

Fewer than 7% of global hotspots for whale-ship collisions have protection measures in place

Oldies but goodies: Study shows why elderly animals offer crucial scientific insights

Math-selective US universities reduce gender gap in STEM fields

Researchers identify previously unknown compound in drinking water

Chloronitramide anion – a newly characterized contaminant prevalent in chloramine treated tap water

Population connectivity shapes cultural complexity in chimpanzees

Direct hearing tests show that minke whales can hear high-frequency sounds

Whale-ship collision risk mapped across Earth’s oceans

Bye-bye microplastics: new plastic is recyclable and fully ocean-degradable

Unveiling nature of metal-support interaction: AI-driven breakthrough in catalysis

New imaging method enables detailed RNA analysis of the whole brain

Stability of perovskite solar cells doubled with protective coating

Chemists create world’s thinnest spaghetti

Empowering neuroscience: Large open brain models released

From traditional to technological: Advancements in fresco conservation

Design and imagination as essential tools during the climate crisis

Innovating archaeology: HKU scholars utilize immersive 3D tech to document and study the human past

What's the story, morning glory?

[Press-News.org] Tumor suppressor forms gel-like assemblies to sacrifice cancer cells