Study uncovers function of mysterious disordered regions of proteins implicated in cancer

A disordered region controls cBAF activity via condensation and partner recruitment

2023-10-02

(Press-News.org) Study uncovers function of mysterious disordered regions of proteins implicated in cancer

Study Title: A disordered region controls cBAF activity via condensation and partner recruitment

Publication: Cell, Monday, October 2, 2023 (https://www.dana-farber.org/newsroom/news-releases/2023/study-uncovers-function-of-mysterious-disordered-regions-of-proteins-implicated-in-cancer/)

Dana-Farber Cancer Institute author: Cigall Kadoch, PhD

Summary:

New research from Dana-Farber Cancer Institute researcher Cigall Kadoch, PhD, along with colleagues at Princeton University and the Washington University in St. Louis, reveals a key role for intrinsically disordered proteins known as IDRs that are implicated in a wide range of human diseases, from cancer to neurodegeneration. Kadoch’s team studies large protein complexes called mSWI/SNF or BAF complexes that control which genes turn on and off in cells. BAF complexes are the most frequently mutated cellular entities, second only to TP53, a tumor suppressor. Intrigued by the fact that over half of the complex mass contains IDRs, including the ARID1A/B subunits in which a high frequency of disease-causing lesions, or mutations, accumulate, the group set out to define their contributions. They found that these IDR regions lead to two important functions: first, condensation, the tight clustering of proteins in close distance to one another in the nucleus, and second, protein-protein interactions that are required for the proper positioning and activity of BAF complexes along DNA. Kadoch and colleagues show that the right interactions depend on highly specific “sequence grammars” within the protein’s IDR amino acid code, a concept broadly useful to the burgeoning area of work in this area to understand and ultimately therapeutically target biomolecular condensates and their constituents.

Impact:

IDRs comprise a large percentage of the human proteome and are particularly important for nuclear proteins that govern our genomic architecture and gene expression. Their disruption is frequent in cancer. This study sheds light on the sequence-specific contributions of IDRs to the highly disease-relevant mSWI/SNF (BAF) chromatin remodeling complexes, which have become top therapeutic targets in oncology.

Funding:

Howard Hughes Medical Institute, The Mark Foundation, National Institutes of Health, United States Air Force Office of Scientific Research, St. Jude Research Collaboratives, Fujifilm, and The Wellcome Trust.

Contact: Cindy Cantrell; cindy_cantrell@dfci.harvard.edu; 781-953-5000

END

[Attachments] See images for this press release:

ELSE PRESS RELEASES FROM THIS DATE:

Liquid biopsy may help identify which patients with non-small cell lung cancer will benefit most from radiation

2023-10-02

SAN DIEGO, October 2, 2023 — A novel liquid biopsy test may help determine which patients with non-small cell lung cancer that has spread beyond the lungs are most likely to benefit from targeted, high-dose radiation, rather than drug-based therapy, a new study suggests. Findings will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting and published in npj Precision Oncology. The study found that a liquid biopsy test – which identifies tumor DNA circulating ...

Pumped for frigid weather: study pinpoints cold adaptations in nervous system of Antarctic octopus

2023-10-02

By Wynne Parry Laden with dissolved salt, Antarctic waters can hover just above freezing and even dip below it. Temperatures this low would likely kill the animals that prosper in warmer waters further north. Yet, some creatures have found ways to live in this inhospitable cold. In a new study described in Proceedings of the National Academy of Sciences, researchers at the Marine Biological Laboratory (MBL) and their collaborators focused on how life in such a frigid habitat has altered an enzyme essential ...

Scientists identify evolutionary gateway helping pneumonia bacteria become resistant to antibiotics

2023-10-02

**Strictly embargoed until 20:00 (BST) Monday 2 October 2023** Scientists identify evolutionary gateway helping pneumonia bacteria become resistant to antibiotics A new study from the University of Sheffield has revealed how pneumonia cells start to become resistant to penicillin antibiotics The effectiveness of antibiotics is increasingly under threat as the bacteria which cause pneumonia become more resistant to antibiotic treatment over time The new research is a major step forward in helping scientists to better predict which ...

How new plant cell walls change their mechanical properties after cell division

2023-10-02

Scientists reveal new plant cell walls can have significantly different mechanical properties compared to surrounding parental cell walls, enabling cells to change their local shape and influence the growth of plant organs. This is the first time that scientists have related mechanics to cell wall “age” and was only made possible through a new method that follows the same cells over time and through successive rounds of division. The Cambridge researchers were able to see new walls forming and then measure their mechanical properties. This pioneering work showed that new cell walls in some plants are 1.5 times stiffer than the surrounding ...

Study shows how ‘superbacteria’ were prevented from spreading in a large tertiary hospital

2023-10-02

Rapid identification of patients contaminated by “superbacteria” known as “carbapenem-resistant Enterobacteriaceae” (CRE), with early isolation of these patients, reduces transmission in hospital emergency departments. However, keeping them in the emergency room (ER) for more than two days undermines containment because it increases the risk of infection via colonization. These are the key findings of a study by a group at the University of São Paulo’s Medical School (FM-USP) in Brazil. An article on the study is published in the journal Clinical Infectious Diseases. Enterobacteria ...

MDMA increases feelings of connection during conversation, showing promise for therapy

2023-10-02

MDMA, commonly known as ecstasy, is a recreational psychedelic drug often used at parties and dance clubs because it creates feelings of closeness and social connection with others. Because of this “empathogenic” effect, researchers are also interested in its potential use as a complement to traditional talk therapy. In fact, two recent successful clinical trials support the use of MDMA-assisted therapy as a treatment for post-traumatic stress disorder (PTSD). Researchers at the University of Chicago published a study in Scientific Reports on September 22, 2023, that looked more closely at the pharmacological ...

Internationally recognized thoracic oncologist Dr. Taofeek K. Owonikoko named Executive Director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

2023-10-02

University of Maryland School of Medicine (UMSOM) Dean Mark T. Gladwin, MD, and University of Maryland Medical Center (UMMC) President and CEO Bert W. O’Malley, MD, announced today that Taofeek K. Owonikoko, MD, PhD, a distinguished physician-scientist with a global reputation in thoracic oncology, has been appointed Executive Director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). Dr. Owonikoko will join the UMSOM faculty as the Marlene and Stewart Greenebaum Professor in Oncology in the Department of Medicine and Executive Director of the UMSOM ...

Meat taxes and other livestock emissions regulations could be feasible, acceptable and effective, argue climate researchers

2023-10-02

Meat taxes and other livestock emissions regulations could be feasible, acceptable and effective, argue climate researchers. #### Article URL: https://journals.plos.org/climate/article?id=10.1371/journal.pclm.0000291 Article Title: High ‘steaks’: Building support for reducing agricultural emissions Author Countries: Germany, UK Funding: This work was financially supported by the Robert Bosch foundation (Junior Professorship grant to LM) The funder had no role in study design, data collection and analysis, decision to publish, ...

Accelerated radiation treatment could reduce head and neck cancer patient burden in low- and middle-income countries

2023-10-02

SAN DIEGO, October 2, 2023 — A type of head and neck cancer predominantly diagnosed in people who reside in low- and middle-income countries may be treated effectively with fewer, but higher doses of radiation, a large new international study suggests. The study – a randomized phase III clinical trial involving 10 countries across four continents – found delivering a course of radiation in 20 rather than 33 treatment sessions was just as effective at controlling cancer for patients with alcohol and tobacco-related, locally advanced disease, without increasing side ...

October issues of American Psychiatric Association journals look at factors influencing depression and PTSD, guidance on handling drugs laced with fentanyl, and more

2023-10-02

The latest issues of three of the American Psychiatric Association’s journals, The American Journal of Psychiatry, Psychiatric Services and The American Journal of Psychotherapy are now available online. The October issue of The American Journal of Psychiatry is focused on research devoted to understanding factors influencing depression, PTSD, and suicidal behavior. Highlights include: Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers. Maternal Perinatal Stress Trajectories and Negative Affect and Amygdala Development in Offspring. Networks of Neurodevelopmental Traits, Socioenvironmental ...

Long-term exposure to air pollution and a lack of green space increases the risk of hospitalization for respiratory conditions

Better cardiovascular health in early pregnancy may offset high genetic risk

Artificial intelligence method transforms gene mutation prediction in lung cancer: DeepGEM data releases at IASLC 2024 World Conference on Lung Cancer

Antibody–drug conjugate I-DXd shows clinically meaningful response in patients with extensive-stage small cell lung cancer

Terasaki Institute awarded $2.3 Million grant from NIH for organ transplantation research using organs-on-a-chip technology

nTIDE September 2024 Jobs Report: Gains in employment for people with disabilities appear to level off after reducing gaps with non-disabled workers

Wiley enhances NMR Spectral Library Collection with extensive new databases

[Press-News.org] Study uncovers function of mysterious disordered regions of proteins implicated in cancer
A disordered region controls cBAF activity via condensation and partner recruitment

Study uncovers function of mysterious disordered regions of proteins implicated in cancer

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: