Hunting down the elusive cytosolic-DNA sensor

• 成果类型: Editorial Material
• 署名作者: Mathis, Diane
• 署名单位: Harvard University; Harvard Medical School
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15125
• DOI: 10.1073/pnas.2415648121
• 发表日期: 2024-09-16
• 关键词: cyclic gmp-amp

摘要

The 2024 Albert Lasker Basic Medical Research Award was attributed to Zhijian (James) Chen for the discovery of the cGAS enzyme that senses foreign and self DNA, solving the mystery of how DNA stimulates immune and inflammatory responses. Bringing to bear an ingenious in vitro complementation system, an astute insight, and superlative biochemistry, Chen and colleagues identified cGAS (cGAMP synthase) as both the molecule that perceives cytosolic DNA in infected, stressed, or dying cells and the enzyme that catalyzes the synthesis of cGAMP (cyclic GMP-AMP), a critical second messenger along the route to inflammatory cytokine production. These findings cleared up the reigning confusion surrounding a major mechanism of inciting the innate immune system, with therapeutic implications for fighting infections, containing tumors, and extinguishing autoimmune and inflammatory diseases.