An amidation a day keeps apoptosis away

Rapidly dividing cells such as tumor cells are susceptible to DNA damage that then induces apoptosis. As a result, DNA-damaging chemicals such as cisplatin are used as anticancer treatments. How the majority of nontumor cells survive chemotherapy has been mysterious. The trivial explanation is that the cells are growth-arrested and thus less susceptible to DNA-damaging agents. But a more precise explanation is put forth in a new article by Benjamin Deverman, Steven Weintraub (Washington University, St. Louis, MO), and colleagues, who have identified an antiapoptotic activity necessary to keep damaged but nondividing cells alive.

The proapoptotic activity that allows tumor cells to die is an unusual modification of the antiapoptotic protein Bcl-x_L caused by DNA-damaging agents. This modification, deamidation of two asparagine residues, inactivated Bcl-x_L, thereby allowing cell death to proceed. Growth-arrested...