Images of protein 'tail' suggest cancer drug target

The researchers report the influence of Ubc12's protein tail is based on its ability to nestle within a groove of the larger molecule called APPBP1-UBA3. These two proteins, also as E2 (Ubc12) and E1 (APPBP1-UBA3), cooperate to form a workshop where the "on switch"​ that accelerates cell replication is constructed.

It has been theorised by the researchers that determining the exact shape and function of the E2 tail and the groove along E1 the tail fits into make these structures potential targets for new drugs.

The workshop makes the switch by linking a tag called NEDD8 with its "target"​ a molecule called Cul1. NEDD8 then modifies Cul1, setting off a set of reactions eliminating the molecular brake controlling cell replication. In the absence of this brake, cell replication accelerates causing cancer.

Danny Huang, first author of the paper said: "Novel drugs that are designed to disrupt the tail, the groove or both might block the ability of the NEDD8 pathway to accelerate replication of cancer cells."​

This latest discovery, made by investigators at St. Jude Children's Research Hospital,​ is published online by the journal Nature Structual and Molecular Biology (NSMB).

The identification of proteins and the roles they play in cancer is seen as the primary point of attack in the fight against cancer. While new therapies are directed at p53, a protein that blocks the development of cancer to its natural inhibitor, new research targets for drug R&D raises hope of finding effective drugs that will work in a broad range of cancer patients.

Scientists at the University of British Columbia recently identified a key regulatory enzyme called protein kinase, which catalyses the processes that regulate a protein's functional activities.

Defects in specific protein kinases have been linked to numerous forms of cancer and about 25 per cent of pharmaceutical research and development is now focused on the discovery and evaluation of protein kinase inhibitors for therapeutic applications.

In addition, the researchers had already identified the JNK and p38 MAPK protein kinases as potential drug targets.

Isis Pharmaceuticals are currently experimenting on antisense inhibition of the drug target Signal Transducer and Activator of Transcription 3 (STAT-3). It is a protein that regulates cell division and growth, and prevents cell death, significantly delayed tumor growth and increased the rate of cancer cell death in multiple cell and animal models of cancer.

According to the market consultants, BCC, the combined market for angiogenesis regulating products was estimated at $100 million (€82 million) in 2001. In 2006, the market for all products regulating angiogenesis is likely to reach $2.4 billion as it grows at an average annual growth rate of over 88 per cent. Currently estimated at $70 million, the market for products, which inhibit angiogenesis, is likely to reach $1.75 billion in 2006.