Researchers find new way to prevent major disease carriers, other mutated genes

ʻIke nā mea noiʻi i ke ala hou e pale ai i ka mea hoʻokele maʻi maʻi nui, nā ʻano gen mutated ʻē aʻe

Abstract images. aie: Website Information (2022). DOI: 10.1016 / j.celrep.2022.110630

CU Boulder researchers have discovered a new way to prevent a common mutated gene under human development, opening the door to new therapeutic approaches for cancer and other diseases. Yes.

The information, published on April 5 in the journal Website Informationsignaling an important step forward in the search for transcription factors (TFs), a complex complex when altered or dysregulated, that can disrupt cell function and drive disease.

“This class of proteins represents one of the highest therapeutic implications in biomedicine,” said senior author and biochemistry Professor Dylan Taatjes. “We are offering a state -of -the -art approach to preventing transcription factor activity that could have wide -ranging applications in many diseases, both in and out of cancer.”

There are more than 1,500 translators in the human body, each responsible for recording specific processes in DNA and translating or “decoding” the body’s genetic makeup. to teach a phone what to do.

Different TFs work on different cell types (flesh, skin, blood, etc.), regulating everything from inflammation to cholesterol metabolism to healing. in controlled cell death, it is the key to preventing cancer.

When a TF is changed, those advice can go wrong, turning a right protein into a bad one “like Jekyll and Hyde,” Taatjes said.

For example, altering the p53 transcription factor, the subject of this study, could change its function from a tumor suppressor to a tumor promoter.

For years, scientists have worked to develop ways to prevent mutated transcription factors. Because they are all similar to pieces of DNA recorded, finding one can directly point to other people, eliminating traditional telephone operations. Translators have a segment, called domain activation, that is isolated in nature, making it difficult for a root to develop to block it.

“However, despite the great power and years of effort, the therapeutic targeting of intractable transcription factors has been proven,” Taatjes said.

It’s a good edit

Taatjes and a team of scientists, including Alanna Schepartz, a professor of chemistry at the University of California, Berkeley, have spent years developing a workaround.

They begin to secrete p53, which is present in all cell types and plays an important role in human growth and the body’s response.

To do so, instead of looking at the p53 itself, they pointed to a 26-subunit complex called the Mediator. Mediator binds to p53 and other receptors, acting as a bridge between them and the enzyme that separates parts of the body’s genetic makeup. Basically, the author needs to click on Mediator, such as a key in a lock, and then start the decoding process.

In recent studies of human cancer cells, the researchers found that when they applied a new peptide, designed to target the p53 activation domain, they could block p53. from work. The team showed that the peptide works by preventing p53 from pressing on the Mediator, such as holding the lock before the real key (p53 itself) can be inserted.

“A ten -year goal is to accurately record drug transcription factors,” Taatjes said. “Here we found a way to have the same functionality as not having to look for a transcription source but a Mediator instead.

Taatjes stressed that the work is a test-of-mind study, and that more research needs to be done before such a design can be implemented in the office.

Finally, he said the pathway could be used to other TFs affected by the disease, opening the door to new treatment initiatives for everything from heart disease to diseases. neurological.

The unique approach they used – using a transcription factor activation domain server as a starting point rather than looking at thousands of compounds – could lead to faster and better pathways. well to develop new guidelines for therapeutics.

“The pathways we’re talking about here could be related to a disease that is driven by aberrant transcription factor activity,” Taatjes said.


The viral pathway for measuring different types of gene modulators


More information:
Benjamin L. Allen et al, Inhibition of the p53 response by locating a p53-mediator that binds to a stapled peptide, Website Information (2022). DOI: 10.1016 / j.celrep.2022.110630

Presented by the University of Colorado at Boulder

Directions: Researchers discover new way to prevent major disease driver, other mutated genes (2022, April 7) Retrieved 7 April 2022 from https://phys.org/news /2022-04-inhibit-key-cancer-driver-mutated.html

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