Nature Cell Biology 1, pp 55 - 59

Transmissible spongiform encephalopathies (TSEs) such as scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and the infamous Creutzfeld-Jakob disease (CJD) in humans, are devastating neurodegenerative diseases. All of these are thought to be caused by a rogue form of normal cellular proteins known as prions.

Different strains of prions are believed to give rise to distinct disease phenotypes. But there is evidence that each strain may simply arise from a different folding — or so-called conformational version — of the same prion protein. But how a single protein can adopt as many different conformations as there are strains of TSEs is a question that has puzzled scientists for sometime. Now, the latest findings of Dr John Collinge, MRC Prion Unit and Department of Neurogenetics, Imperial School of Medicine at St Mary's and colleagues, may provide an explanation.

Collinge's group present evidence that copper (whose unbound concentrationin the brain is unkown) may influence the shape of the abnormal prion protein, essentially causing the prion to switch from one strain to another. This provocative link between the metal-binding capabilities of prion protein and strain variations raises the possibility that drugs which influence copper metabolism may have therapeutic potential in prion diseases.

Nature Cell Biology 1, pp 20 - 26

p53 is a crucial 'tumour suppressor' protein. It is frequently altered or missing in human tumours - indeed the loss of p53 function is thought to cause, or at least contribute to, the development of many different types of human cancer. Thus, as an essential part of the normal life cycle of every cell, p53 needs to be very tightly controlled.

Over the past few years, a complex picture of p53 regulation has emerged. Now, Dr Charles Sherr (St. Jude Children's Research Hospital,TOWN, COUNTY) and Dr Dafna Bar-Sagi (SUNY at Stony Brook, TOWN, COUNTY) and colleagues, present a new finding which promises to deepen our understanding of this vital control process.

Mdm2, which was originally identified as a cancer-causing gene, or 'oncogene', disrupts p53 function. Sherr and Bar-Sagi have discovered how, in healthy cells, this protein is kept in check. They show that another protein, called ARF which is itself known to be a tumour suppressor protein, actually traps the oncogenic mdm2 in nucleoli - sub-chambers within the cell nucleus - from whence it can no longer block p53.

The elucidation of this mechanism suggests that mutations in ARF that prevent it from trapping mdm2 may, like p53 alterations themselves, disrupt the 'anti-cancer' function of p53 and hence contribute to human tumour formation.

Nature Cell Biology 1, pp 60 - 67

For centuries, traditional Chinese herbal medicines have been used to treat a vast array of conditions. These medicines are usually a mixture of many components and often it is not clear which ingredients are the active ones or how they work. One such mixture is Danggui Longhui Wan, an ancient and surprisingly effective treatment for several leukemias.

Recently, scientists have postulated that the active ingredient in Danggui Longhui Wan is indirubin, the red coloured relative of the indigo blue dye. Now, Laurent Meijer and colleagues at the C.N.R.S., Roscoff, France, reveal a molecular mechanism by which indirubin appears to stop the uncontrolled growth of tumour cells.

They found that indirubin interacts with a class of proteins known as cyclin dependent kinases. These enzymes lie at the heart of the machinery that dictates whether-, and when a cell divides. When indirubin binds to these kinases it blocks their activity and hence halts cell division. Meijer's group have also determined the molecular structure of a complex molecule comprised of cyclin dependent kinases bound to indirubin. This structure sheds light on how exactly indirubin is able to specifically impede the function of these enzymes but not others like them. It is hoped that these insights into the way indirubin — and, indeed, Danggui Longhui Wan — works may feed into the search for better anticancer drugs.