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© The Rockefeller University Press, 0021-9525/2002/10/201-a $5.00
The Journal of Cell Biology, Volume 159, Number 2, 201-a-201

An amidation a day keeps apoptosis away

Bcl-xL modification by cisplatin is blocked by Rb. Weintraub/Elsevier

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 cells escaped apoptosis by blocking deamidation. To prevent deamidation, cells needed Rb, a tumor suppressor protein that inhibits cell cycle progression. Because tumor cells lack Rb, and cycling cells down-regulate Rb, they are more sensitive to DNA-damaging agents. "Deamidation is like a checkpoint," says Weintraub. "If you undergo DNA damage in the absence of Rb, then cells are susceptible to death."

Reference:

Deverman, B., et al. 2002. Cell. 111:51–62.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 315K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?