Arsenic has been used for centuries as a medical treatment, and in the form of arsenic trioxide, it’s currently a highly effective FDA-approved treatment for a type of leukemia. Chinese researchers led by Sai-Juan Chen and Zhu Chen of Shanghai Jiao Tong University School of Medicine have now determined that As2O3 works by binding to a cysteine-rich region of a key protein found in promyelocytic leukemia patients, initiating a chain of events that leads to degradation of the protein (Science 2010, 328, 240). The protein involved is a fusion protein that results from a chromosomal translocation found in more than 98% of human acute promyelocytic leukemia cases. The translocation combines the genes of promyelocytic leukemia protein (PML), which is believed to be involved in regulating cell growth and death, and retinoic acid receptor alpha. The researchers found that As2O3 binds to cysteine-rich “zinc finger” regions of PML’s N-terminal domain. They propose that the resulting conformational changes lead to protein oligomerization and certain posttranslational modifications that trigger the protein’s degradation.