Please quote Nature Cell Biology as the source of these items.

The May 2004 issue of Nature Cell Biology is available online.

Nature Cell Biology 6, pp 458 - 464

The sperm that initially emerge from the mammalian testis cannot swim or fertilize an egg. Passage through a specialized organ — termed the epididymis — is required to complete the maturation process, but exactly how this occurs remains unclear. Now research in the May issue of Nature Cell Biology from Chang Chan and colleagues shows that a protein important for defence against pathogens may also be required for sperm maturation, suggesting a possible common basis for some sexually transmitted diseases (STDs) and infertility.

β-defensins are short proteins known for their protective action against microbes. The researchers now show that a rat b-defensin, Bin1b, binds to sperm and is critical for normal sperm maturation in rats. In the absence of Bin1b, the movement of sperm from the epididymis is severely impaired.

This work demonstrates that the function of defensin molecules is probably not restricted to host defence, but might also be required for sperm maturation. As these defensins are also present in the epididymis of humans, they might present a potential new therapeutic target in the treatment of both STDs and infertility.

Nature Cell Biology 6, pp 436 - 442

Adult stem cells offer great therapeutic potential for a variety of diseases through their capacity to replenish diseased cells and tissue. At present, however, it remains a real challenge to induce efficient repopulation of target tissues by stem cells. Now, research in the May issue of Nature Cell Biology shows that bone marrow stem cells from mice, missing a gene known to inhibit cell division, can overcome this hurdle to a great extent.

Tao Cheng and colleagues used mutant mice lacking a protein, p18, which normally inhibits cell division in mammalian cells and is implicated in several cancers. They find that, compared with normal stem cells, the stem cells isolated from this mutant are much more efficient at repopulating an injured bone-marrow tissue. This was apparently due to increased division of the mutant stem cells, resulting in a larger cell population and thus a competitive advantage.

It seems that the p18^INK4C protein normally inhibits the division and self-renewal of bone-marrow stem cells, and so blocking its function may be a productive way to enhance the efficacy of stem cell transplantation in disease models.

Nature Cell Biology 6, pp 443 - 450

The p53 protein is a key factor in the body's natural defence against cancer. Under normal conditions, it initiates death in cells that have begun to divide uncontrollably, mainly by increasing expression of genes that cause cell death. However, research in this month's Nature Cell Biology suggests that p53 performs a more direct role in cell suicide (apoptosis) by interacting with one of the pro-death proteins.

Donna George and colleagues show that some of the cancerous mutations in p53 lie in a region that is important for interactions with the BAK pro-death protein. BAK mediates cell death by piercing holes in mitochondria, resulting in the release of other pro-death proteins that initiate apoptosis. The p53-BAK interaction also prevents BAK from interacting with an anti-death protein that normally prevents BAK from attacking mitochondria. Thus, p53 may induce cell death by interfering with this protective interaction.

Given the prevalence of defective p53 in various cancers, understanding the specific interactions that mediate its function may be the key to future cancer treatments. Drug- or gene-therapy-based treatments that focus on the interaction of p53 with these pro-death proteins should provide exciting alternatives to current cancer therapies.