New research from NYU Abu Dhabi could create cancer
Abu DhabiMay 25, 2022: A team led by Professor of Biology, Senior Vice-Rector for Research at NYU Abu Dhabi and Sehamuddin Galadari, a national of the United Arab Emirates, discovered a novel structural modification of AMP-activated protein kinase (AMPK) over the course of cancer therapy that could pave the way for the development of more effective cancer treatments.
AMPK normally functions as a cellular energy sensor that is activated when there is a shortage of energy in the body. Once activated, AMPK triggers events in the cell that restore energy balance. The main component of AMPK exists in two isoforms (functionally similar proteins) – AMPK-⍺1 and AMPK-⍺2.
In an article titled Caspase cleavage and nuclear retention of AMPK-α1 energy sensor during apoptosis in Cell reports, the research team identified that the enzyme caspase-3 specifically cleaves AMPK-⍺1 (but not -⍺2) during cancer treatment. The scientists also identified the precise location of truncation – the process of shortening something by removing part of it – and found that, as a result, cleaved AMPK-⍺1 is trapped in the cell nucleus.
The results are of significant clinical and biological importance as they will help researchers design and develop a drug that specifically targets nuclear-cleaved AMPK-⍺1, which could increase the effectiveness of chemotherapy or existing radiotherapy.
Commenting on the results, Galadari said: “Despite advances in biomedical research and clinical applications, cancer remains one of the leading causes of death worldwide. Most cancer drugs work by inducing the death of cancer cells. However, resistance to treatment continues to be the biggest limiting factor in achieving cancer cures. In our work based on cell culture models, we noticed that nuclear-retained cleaved AMPK-⍺1 confers protection against cancer drug-induced cell death, causing resistance to chemotherapy.
The study was carried out in collaboration with Professor Grahame Hardie from the School of Life Sciences at the University of Dundee. Hardie, a pioneer in AMPK research, discovered and defined AMPK in the 1980s and characterized several of its functions.
NYUAD researcher and lead author of the paper, Faisal Thayyullathil, commented, “Interestingly, the gene encoding AMPK-α1 is frequently amplified in human cancers. Our results suggest that genomic instability in such tumors could precipitate caspase cleavage and nuclear retention of amplified AMPK-α1, thereby protecting tumor cells from cell death.”
Anees Rahman, NYUAD researcher and first author of the paper, added, “A better understanding of the compartment-specific functions of cleaved AMPK-α1 will help us develop strategies to optimize the clinical outcomes of therapeutic interventions.”
About NYU Abu Dhabi
NYU Abu Dhabi is the first comprehensive liberal arts and sciences campus in the Middle East to be operated overseas by a major American research university. NYU Abu Dhabi has integrated a highly selective liberal arts, engineering, and science curriculum with a global center for advanced research and scholarship enabling its students to succeed in an increasingly interdependent world and advance the cooperation and progress on the common challenges of humanity. High-achieving students at NYU Abu Dhabi come from 115 countries and speak more than 115 languages. Together, NYU’s campuses in New York, Abu Dhabi and Shanghai form the backbone of a unique global university, offering faculty and students the opportunity to experience diverse learning environments and immersion in other cultures. on one or more of the many study abroad sites that NYU maintains. on six continents.
The title of the article
Caspase cleavage and nuclear retention of AMPK-α1 energy sensor during apoptosis
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