Blocking carcinogenic proteins: new progress in fighting cancer

New findings from the Journal of natural chemistry and biology show that they hope to find new ways to treat lung cancer and other deadly diseases Kentucky continues to rank the top of the national lung cancer incidence rate and mortality rate University of Kentucky is committed to reducing these figures According to the National Cancer Institute, cancer is one of the leading causes of death worldwide Among those diagnosed in the United States, lung cancer accounts for 25 percent of cancer deaths The numbers are clear: one in two patients diagnosed with lung cancer will not survive for 12 months To solve this problem, the collaboration between scientists at the University of Kentucky School of medicine, the memorial hall of the Sloan Caitlin Memorial Center and the St Utah children's research hospital has enabled researchers to move forward to a new solution A compound developed by Dean Kip guy's British College of Pharmacy Laboratory, whose research started in St Juda children's research hospital, now provides us with a new way to block carcinogenic proteins at the cellular level Ten years ago, the study began on the basis of Dr bhuvanesh Singh, a physician scientist at the memorial Sloan Kettering cancer center, who found that the increase of protein expression called dcn1 can lead to the development of more malignant lung cancer and shorten the life span of patients Among the patients he studied, those with high levels of dcn1 expression died faster than those with normal levels Through this dismal finding, singer's team began to study the specific details of dcn1 Although dcn1 is a normally produced protein in the human body, his team found that too much of this protein directly leads to cancer formation Simply put, when the amount of dcn1 in cells increases, malignant tumors will form As a result, dcn1 patients with higher levels of body disease progress faster and die faster Brenda Shulman's lab, led by biochemist Dennis Scott, has worked hard to explore how dcn1 interacts with other proteins and controls cellular processes Using X-ray crystallography, they found that a small modification of dcn1 (known as ube2m) was necessary This modification, N-terminal acetylation, has not previously been shown to be essential to control the activity of this specific protein Recognizing that it is possible to conduct research on this modification process, Shulman reached out and established cooperation among three laboratories Their goal is to develop a way to prevent dcn1 from killing patients Understanding the behavior and functionality of DCN1 is far more useful than running simple tests Understanding how proteins in cells work is a major step forward Based on Schumann's team's scientific research, Jared Hammill from guy's lab and Danny Scott from Schumann's lab worked together to stop the interaction of dcn1 If the activity of dcn1 depends on this interaction, then it means that they can create a mixture to prevent this interaction Guy describes this interaction as "locks and key models." Scientists have a blank key - this is ube2m, and a lock is dcn1 The key is to be put into the lock, so it is modified until it can fit into the lock The modification process is N-terminal acetylation "What's the point?" said guy "Well, we're the first team to show that protein interactions controlled by N-terminal acetylation can be blocked We basically block locks with compounds, so the bonds won't fit." The stuck object is a series of small molecules created in the laboratory When molecules are tested directly in cancer cells, they work They effectively block the combination of dcn1 and ub2em After decades of collaborative research, there is finally an obstacle between locks and keys The impact of these findings on health care and lung cancer patients may be profound "We are excited about the impact of this study, which provides us with meaningful solutions to diseases such as cancer, neurodegenerative diseases and infections." Schulman said "It's exciting to work with a lot of complementary professional teams, and this research has opened many new doors for us." Cooperation among the three laboratories may mean that many people with various diseases will be treated "It's really exciting to spend decades on this research and achieve such promising results," Singh said "Finally, the most important thing is to improve the health outcomes of patients This work represents an important step in the development of new methods to treat the most difficult cancers and hope to improve the cure rate."