Nature Cell Biology doi: 10.1038/ncb1211

A defining characteristic of stem cells is that they are able to self-renew by cell division for prolonged periods while maintaining the ability to differentiate into multiple cell types. A new study in the January issue of Nature Cell Biology, finds that p53 - known for its master regulatory role as a tumor suppressor - can also switch off self-renewal and initiate differentiation in mouse embryonic stem cells. Given p53’s ability to sense toxic insults and DNA damage, these findings suggest that p53 may protect the genetic stability of stem cells by inducing differentiation and subsequent cell death of defective stem cells.

p53 mediates most of its effects by regulating the expression of genes. Xu and colleagues, found that p53 turned off the Nanog gene, which is known to be necessary for self-renewal of embryonic stem cells. Loss of Nanog leads to the differentiation of the embryonic stem cells. Nanog is known to be important for regulating stem cell proliferation in the early embryo, but it’s unclear at this point whether or not its regulation by p53 is important for early development.

The therapeutic potential of human embryonic stem cells has generated a lot of interest into the molecular machinery that regulates their self renewal, and these findings identify an important new player for investigation.

Nature Cell Biology doi: 10.1038/ncb1215

As we age, the chances of developing tumours increase. While this commonly known characteristic seems to make sense, it is actually a paradoxical observation: ageing cells undergo an irreversible growth arrest but cancer is characterized by uncontrolled cell growth. A report published in Nature Cell Biology by You and colleagues now shows that growth arrest in aging cells might directly lead to cell cancer formation explaining this apparent contradiction.

During the lifetime of a cell, its DNA is constantly damaged by environmental factors like smoking or radiation. This would cause mayhem in our genetic code, leading to a high rate of tumour formation in all of us, if we did not have sophisticated DNA repair systems that can reverse this damage. Nevertheless, some cells struggle to keep up with the ongoing repairs and acquire mutations that can lead to uncontrolled cell growth. To circumvent tumour formation, these cells are normally programmed to commit suicide - a safety mechanism called apoptosis.

You and colleagues have now investigated the human gene Bcl-2, which surprisingly has the ability to both inhibit apoptosis (supporting tumour formation) and induce cell growth arrest (inhibiting tumour formation). They explain this contradiction by showing that the Bcl-2-induced cell growth arrest does not necessarily protect these cells from becoming cancerous, as commonly thought. Rather, it causes inhibition of a DNA repair mechanism called mismatch repair and this subsequently leads to a dramatic accumulation of mutations and carcinogenesis.

This discovery links cell growth arrest - mainly seen in ageing cells - with carcinogenesis and so sheds new light on the development of human cancer.