- College of Pharmacy at Catholic University, Professor Yong-Yeon Cho's team reveals molecular 

  mechanism of Karyoptosis... Unveils a new pathway for cancer cell demise through induced nuclear 

  membrane rupture 

- Research results published online in the prestigious international journal "Experimental & Molecular Medicine

  (IF 12.8)"

*Figure: Actual image frames demonstrating Karyoptosis induction. With CREB3-CF overexpression, an explosive rupture of the nuclear membrane can be observed (frame 4). As a result, we can confirm the process of cell death (frame 5) where the contents of the nucleus burst out and collapse.

 Professor Yong-Yeon Cho's research team at the College of Pharmacy, Catholic University (President Jong-chul Won), has globally identified, for the first time, the molecular mechanism of a new cell death method named "Karyoptosis," triggered by the protein CREB3. This breakthrough is expected to contribute to the development of various treatments and therapeutic agents by being utilized as a method for destroying diseased cells, such as cancer cells, that cause human diseases.

 The nuclear membrane is a frontline apparatus that regulates the exchange of substances and signals between the nucleus and cytoplasm, remodeling of fixed chromatin, and gene expression. It is an intracellular device that controls cell survival, differentiation, and death. When its integrity is compromised due to excessive stress, genetic damage, unfolded protein responses, or cellular movements, it prompts cell demise. While the deterioration of nuclear membrane integrity has long been linked to various diseases, the factors causing it, the process of cell demise, and the molecular mechanisms involved remained elusive.

 In 2018, Professor Manolis Fanto of King's College London discovered autophagy, a process that clears toxic proteins and is chronically suppressed in patients with degenerative brain diseases. This led to anomalies in the nuclear membrane and genome leakage, which he termed "Karyoptosis." However, the causal genes and proteins for Karyoptosis, as well as the molecular mechanisms leading to nuclear membrane rupture, remained unknown.

 Professor Yong-Yeon Cho's team, engaged in research on signal transmission networks and protein interactions during cancer onset and anti-cancer processes, found that CREB3-CF, known as a type II membrane-embedded protein and genetic transcription factor, induces nuclear membrane rupture and genome leakage, ultimately causing cell demise. 

 This study is the world's first to elucidate, through real-time video recording and molecular mechanism research, that the protein CREB3 interacts with chromatin at the nuclear membrane, tethering the chromatin to the nuclear membrane. When CREB3 fragmentation occurs due to stimuli that induce loss of integrity, the balance between the expansive force of the genome within the nucleus and the restraining force that prevents the nuclear membrane from bursting using chromatin is disrupted. This leads to the rupture of the nuclear membrane and subsequent cell death. Thus, this research has demonstrated for the first time in the world how Karyoptosis is induced by genes and proteins, and what its molecular mechanism is

 The team predicts that the impact of cell demise through Karyoptosis equals or exceeds that of other extensively researched cell death mechanisms such as apoptosis, autophagy, and necroptosis, affecting approximately 16-40% of cases. Given the elucidation of the relationship between nuclear membrane integrity control and disease onset, this research is poised to serve as a foundational technology for developing various therapies and therapeutic agents for human diseases. 

 Supported by △the Ministry of Science and ICT and the Korea Research Foundation's Mid-Career Researcher Support Program, △International Collaboration Joint Research Support Program with King's College London, this research has been published online in the esteemed international academic journal "Experimental & Molecular Medicine (IF 12.8)" and has received high acclaim.

 Dean Yong-Yeon Cho of the Catholic University's College of Pharmacy stated, "The integrity of the nuclear membrane and gene expression through chromatin remodeling in response to various and complex intracellular conditions are the most crucial aspects of maintaining life and the basis of homeostasis." He added, "We hope that the molecular mechanism of maintaining nuclear membrane integrity through the protein CREB3, which we have elucidated in this study, can be utilized as a foundational technology for developing treatments and therapeutic agents for various human diseases." (End of Document)