Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 645K) 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 Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Related Collections Related Article Social Bookmarking                            What's this?

Caspase-free mitotic death

DNA (blue) breaks up as a cell with a faulty spindle checkpoint prepares to kill itself.

On page 283, Niikura et al. document a new way for abnormal cells to kill themselves. The mechanism might weed out potentially cancerous cells in which the spindle checkpoint has malfunctioned.

Before progressing through mitosis, cells verify that the microtubules of the spindle apparatus are properly attached to the chromosomes. If they aren't, the spindle checkpoint kicks in, halting mitosis to permit repairs. If the spindle checkpoint goes awry, cells can amass extra chromosomes and become cancerous. Apoptosis disposes of many of these aneuploid cells during the next G1 phase. Niikura et al. wanted to find out whether spindle checkpoint defects can also trigger cells to die during mitosis.

The researchers used RNAi to cut cells' output of the checkpoint protein BUB1. Three drugs that disrupt the kinetochore–microtubule connection spurred these cells to expire during mitosis. Like victims of apoptosis, BUB1-deficient cells harbored fractured DNA. However, their demise didn't involve caspase enyzymes, suggesting that this type of cell suicide—which the researchers dubbed caspase-independent mitotic death (CIMD)—is distinct from apoptosis. CIMD doesn't depend on p53, which prompts cells with DNA damage to take their own lives, but does require its cousin p73. The results indicate that cells have a mitotic self-elimination mechanism in case the spindle checkpoint falters. Some details of CIMD remain mysterious, however. For example, the researchers are now investigating why CIMD can occur if BUB1 levels are low, but not if the protein is altogether absent.

Mitch Leslie

mitchleslie{at}comcast.net

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

BUB1 mediation of caspase-independent mitotic death determines cell fate

Yohei Niikura, Amruta Dixit, Ray Scott, Guy Perkins, and Katsumi Kitagawa
J. Cell Biol. 2007 178: 283-296. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 645K) 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 Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Related Collections Related Article Social Bookmarking                            What's this?