Ground truth image frame in which carryoptosis is induced. (provided by Università Cattolica)/News 1
A national research team has identified the cause of nuclear membrane breakdown, laying the foundation for preventing human diseases, including cancer, and developing new treatment technologies.
The National Research Foundation of Korea announced on the 28th that the research group of Professor Cho Yong-yeon of the Catholic University has identified the molecular mechanism of “carryoptosis”, a new method of cell death triggered by the CREB3 protein.
The nuclear membrane surrounding the cell nucleus plays a role in the exchange of materials and signals into and out of the nucleus, in the remodeling of chromatin, the main component of chromosomes, and in the regulation of gene expression.
However, when the nuclear membrane loses its integrity during genetic damage, unfolded protein stress, and cell migration, it induces cell death.
Carryoptosis, first reported in the UK in 2018, is known to be characterized by cell death due to disruption of the nuclear membrane, exposure of the genome within the nucleus and activation of DNA damage signaling, but the cause of the loss of nuclear membrane integrity, the resulting cell death process and the molecular mechanism has not been identified.
As a result, the research team captured the world’s first actual measurement image of the process of karyoptosis, in which the nuclear membrane breaks down, the genome in the nucleus leaks, DNA is damaged and the cell dies, and the molecular mechanism.
The research team found that CREB3, a type 2 intramembrane protein, plays a role in tethering chromatin to the nuclear membrane, and when segmentation occurs in CREB3 through an anomalous method such as an external stimulus, the balance between the expansion force of the genome into the nucleus and the binding force to prevent rupture of the nuclear membrane are lost. It was confirmed that cell death occurred when the nuclear membrane ruptured and exploded.
Furthermore, carryoptosis was revealed to be an independent cell death as it does not overlap with biomarkers such as apoptosis and self-purging, which are known as existing methods of cell death.
The influence of carryoptosis on cell death (the proportion of cells killed by carryoptosis in the total cell population) was approximately 16–40%, which was similar to or higher than existing regulated cell death methods such as self-purging.
Cho Yong-yeon, professor at the Catholic University. /News 1
Professor Cho Yong-yeon said: “This study is significant in identifying the mechanism for maintaining the integrity of the nuclear membrane, which is the source of control of life” and “The molecular mechanism for maintaining the integrity of the nuclear membrane through CREB3 Proteins are a source for developing cures and treatments for various human diseases. “I hope they can be used as a technology,” he said.
The results of this research, conducted through a mid-career researcher support project supported by the Ministry of Science and ICT and the National Research Foundation of Korea, were published online in ‘Experimental Molecular Medicine’, a journal of the Society Korean Biochemistry and Molecular Biology, the 13th.
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