Nav: Home

New role for death molecule

February 11, 2019

PHILADELPHIA - Cellular death is vital for health. Without it, we could develop autoimmune diseases or cancers. But a cell's decision to self-destruct is tightly regulated, so that it only happens to serve the best interests of the body. Now researchers have discovered a novel role for a signaling molecule that was once considered a dispensable player, a discovery that could inform fields of research as diverse as cancer, autoimmunity, and in-utero development. The research was published in Nature Communications, February 11th.

Years ago, researchers in the field discovered receptors on the surfaces of cells they called "death receptors." These molecules would send the cell into a cascade of cellular reactions that ended in death. Soon after, three molecules were discovered that contained "death domains," areas on the molecule that directly interacted with the death receptors and helped relay the message. These molecules proved so essential that without them mice lacking these death-domain molecules died young. At least that was the case in two of the three molecules.

Of the three major death-relaying molecules, RIPK1, FADD, and TRADD, it seemed TRADD was less essential. Without FADD, mice died in utero. Without RIPK1, mice die shortly before or after birth. Without TRADD, mice seemed to do just fine. TRADD had a death domain - it clearly was connected to cell-death pathways - but its main purpose was unclear.

Senior author, Jianke Zhang, PhD, a Professor of Microbiology and Immunology at Jefferson (Philadelphia University + Thomas Jefferson University) has been studying cell-death pathways for decades. Through the work of Dr. Zhang and others, it became clear that the roles of these molecules wasn't simply to turn on the death signal. Rather, in certain combinations they could protect a cell from death, rather than spur suicide.

Through the work of first author and postdoctoral fellow John Dowling, their most recent paper, the researchers showed that TRADD serves a dual function. In cells lacking the RIPK1 protein, having two copies of the gene TRADD or no copies of it would result in cell death. On the other hand, when only one copy of TRADD gene was present in cells lacking RIPK1, the cells tended to turn off the death signal, and promote cell survival.

"The work sheds new light on the regulation of cell death and survival," said Dr. Zhang. "In certain contexts, such as in cells that have naturally low RIPK1 expression, TRADD could drive death or promote survival."
-end-
Article reference: John P. Dowling, Mohamed Alsabbagh, Christina Del Casale, Zheng-Gang Liu, Jianke Zhang, "TRADD regulates perinatal development and adulthood survival in mice lacking RIPK1 and RIPK3," Nature Communications, DOI: 10.1038/s41467-019-08584-5, 2019.

Media Contact: Edyta Zielinska, 215-955-7359, edyta.zielinska@jefferson.edu.

Thomas Jefferson University

Related Cell Death Articles:

New players in the programmed cell death mechanism
Skoltech researchers have identified a set of proteins that are important in the process of apoptosis, or programmed cell death.
Tumors hijack the cell death pathway to live
Cancer cells avoid an immune system attack after radiation by commandeering a cell signaling pathway that helps dying cells avoid triggering an immune response, a new study led by UTSW scientists suggests.
How trans fats assist cell death
Tohoku University researchers in Japan have uncovered a molecular link between some trans fats and a variety of disorders, including cardiovascular and neurodegenerative diseases.
Bacteria can 'outsmart' programmed cell death
To be able to multiply, bacteria that cause diarrhoea block mediators of programmed cell death, a new study in 'Nature Microbiology' shows.
Breaking the dogma: Key cell death regulator has more than one way to get the job done
Immunologists from St. Jude Children's Research Hospital have revealed two independent mechanisms driving self-defense molecules to trigger cell death.
Cell death or cancer growth: A question of cohesion
Activation of CD95, a receptor found on all cancer cells, triggers programmed cell death -- or does the opposite, namely stimulates cancer cell growth.
Cell death blocker prevents healthy cells from dying
Researchers have discovered a proof-of-concept drug that can prevent healthy cells from dying in the laboratory.
Road to cell death mapped in the Alzheimer's brain
Scientists have identified a new mechanism that accelerates aging in the brain and gives rise to the most devastating biological features of Alzheimer's disease.
Preventing cell death as novel therapeutic strategy for rheumatoid arthritis
A collaborative study by research groups from the University of Cologne, VIB, Ghent University, the Βiomedical Sciences Research Center 'Alexander Fleming' in Athens and the University of Tokyo identified a new molecular mechanism causing rheumatoid arthritis.
Atherosclerosis: Induced cell death destabilizes plaques
Many chronic disorders arise from misdirected immune responses. A Ludwig-Maximilians-Universitaet (LMU) in Munich team led by Oliver Söhnlein now shows that neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death and that a tailored peptide inhibits the process.
More Cell Death News and Cell Death Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.