q&more
My watch list
my.chemie.de  
Login  

News

Protein BRCA1 as a Stress Coach

Christina Klotz / JMU

Cells of a neuroblastoma: The red dots mark sites where the BRCA1 protein occurs in close contact with the RNA polymerase II. This is only the case if the protein MYCN is also present (right).

22-Mar-2019: Two proteins work hand in hand to ensure that the tumour cells of neuroblastoma can grow at full speed. In "Nature", a Würzburg research team shows how the proteins can do this.

Anyone who has ever studied the molecular basis of breast cancer will probably have heard of the abbreviation BRCA1 – this is a protein that protects the cells of breast tissue against cancer. Surprisingly, this protein can also have an opposite effect: In another type of cancer, neuroblastoma, it helps to keep the tumour stable.

Neuroblastoma is a cancer that occurs in early childhood. Degenerate cells of the nervous system grow into tumours in the abdominal cavity; the disease can progress very differently. Less aggressive tumours can be treated well or disappear spontaneously. On the other hand, the survival prospects for children whose cancer cells contain the tumour protein MYCN are particularly poor.

Investigations on cell cultures and patients

"In aggressive neuroblastomas, the tumour protein MYCN must interact with BRCA1 in order to keep the tumour alive," says Dr. Steffi Herold, a researcher in Professor Martin Eilers' research group at the Biocenter of Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany. The group discovered this in cell culture experiments.

The results were also confirmed in tissue material from patients: Tumours of children, which contain MYCN, always have high concentrations of BRCA1. This was shown by researchers from Amsterdam and Utrecht, who are cooperating with Eilers' group.

In a publication in “Nature”, the JMU team describes the mechanism by which the BRCA1 protein keeps neuroblastoma cells alive. Because cancer cells grow far too fast and divide far too often, they have to run their metabolism at very high speed. This means stress for the cells, and this is where BRCA1 comes in: "Put simply, it ensures that the cells are able to cope with this stress," explains JMU postdoc Dr. Gabriele Büchel.

BRCA1 opens a side track in the event of damage

More precisely: In the cells of the neuroblastoma, now the protein MYCN controls transcription, i.e. the reading of genetic information in the cell nucleus. Professor Eilers compares this process, which is essential for the survival of the cell, with a train running on a track. "If the track is damaged, the train comes to a standstill. The growth of the tumour cell stops, it threatens to die." In this case, the protein BRCA1 ensures that a switch to a side track is opened. There, the train can wait until the tumour cell has repaired the damage on the main track.

So the proteins MYCN and BRCA1 work hand in hand to ensure that the metabolism of tumour cells can continue to run at full speed. The JMU team became aware of this when they looked for previously unknown targets in neuroblastoma cells that could be used to inhibit tumour growth.

Many other questions need to be clarified

Although patients with neuroblastoma will not benefit immediately from the new findings, the Eilers team will pursue the topic. They expect that the findings will contribute to the development of new therapies for this disease. They also hope to clarify whether MYCN and BRCA1 proteins only work together in neuroblastomas or whether there is a general mechanism that also affects other types of cancer. Dr. Herold will analyse for instance prostate cancer cells because the MYCN protein is also associated with a highly aggressive form of these tumours.

PhD student Jacqueline Kalb will focus on the exact mechanism of cooperation between the two proteins and whether proteins other than those described in "Nature" are involved. And Dr. Büchel will investigate neuroblastomas driven by MYCN in order to find out whether their stress situation can be exploited to improve therapies.

Original publication:
"Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA Polymerase"; Nature; 20 March 2019 (AOP)

Facts, background information, dossiers

  • proteins
  • neuroblastoma
  • cancer
  • cellular stress

More about Uni Würzburg

  • News

    Inert Nitrogen Forced to React with Itself

    Direct coupling of two molecules of nitrogen: chemists from Würzburg and Frankfurt have achieved what was thought to be impossible. This new reaction is reported in Science magazine and opens new possibilities for one of the most inert molecules on earth. Constituting over 78 % of the air ... more

    New findings about anti-malaria drug

    Artemisinin is derived from the leaves and flowers of the annual mugwort (Artemisia annua) and has been used in traditional Chinese medicine for centuries. The effectiveness was investigated by the Chinese researcher Tu Youyou. Her research was 2015 rewarded with the Nobel Prize. Artemisini ... more

    Progress in Super-Resolution Microscopy

    Does expansion microscopy deliver true-to-life images of cellular structures? That was not sure yet. A new publication shows for the first time that the method actually works reliably. Immersing deeper and deeper into cells with the microscope. Imaging the nucleus and other structures more ... more

  • q&more articles

    High-tech in the beehive

    Healthy honeybee colonies are crucial to maintaining the natural diversity of flowering plants and the global production of plant-derived foodstuffs. As much as 35 % of this production depends on insect-based pollination, in which the honeybee (Apis mellifera) plays a leading role. For fund ... more

  • Authors

    Prof. Dr. Jürgen Tautz

    studied biology, geography and physics at the University of Konstanz before receiving his doctorate from the University on an ecology-related subject. Work in insect, fish and frog bio-acoustics was followed by his foundation of the BEEgroup at the University of Würzburg in 1994, a group th ... more

  • Videos

    High-tech in the beehive

    more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by:

 

Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE