By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.
Wounded mice lacking molecules that manage cellular responses to thrombin ¿ an enzyme in the clotting cascade, which converts fibrinogen to fibrin ¿ bleed longer. The good news is that they seem to be protected from thrombosis, the clotting that obstructs blood flow. Working together, fibrin and platelets create a plug that prevents bleeding long enough for healing to take hold. The bad news is that clots can also form in blood vessels scarred by cholesterol-laden atherosclerotic plaques. These slow or stop blood flow, leading to heart attacks and strokes.
Back to the good news: A protein called PAR4 ¿ protease-activated receptor ¿ seems essential for thrombin to activate platelets and keep clotting normal in mice. A paper in Nature, dated Sept. 6, 2001, explores this PAR4 connection under the title: ¿Role of thrombin signaling in platelets in hemostasis and thrombosis.¿ Its senior author is cardiovascular researcher Shaun Coughlin at the University of California at San Francisco.
An accompanying editorial finds that the results from the Nature paper ¿provide a conclusive demonstration of the essential role of PAR4 in the activation of platelets by thrombin and, by extension, of the need for thrombin itself.¿ It concludes that the article ¿also re-emphasizes the possibility that drugs that block PAR1, PAR4 or both might be useful in treating a variety of clotting disorders in humans.¿
Just a week earlier, an article in Science, dated Aug. 31, 2001, covers the same ground at the prenatal level. It¿s titled: ¿A role for thrombin receptor signaling in endothelial cells during embryonic development.¿ That paper¿s senior author is the same Shaun Coughlin at UCSF.
Gift of Second Site On Key Enzyme Speeds Transcription, May Help Cancer Research
When a previously unknown chemical site on the key enzyme RNA polymerase is occupied, it speeds up the process by which RNA converts information in DNA into functions critical for maintaining life. When the precursor molecule does not occupy the site, the enzyme copies the DNA slowly. When it does, RNA production kicks into overdrive ¿ occurring about 10 times faster than before. The finding is reported by the journal Cell in a paper titled: ¿Allosteric binding of nucleoside triphosphates to RNA polymerase regulates transcription elongation.¿ Its senior author is chemist Dorothy Erie, at the University of North Carolina at Chapel Hill.
¿Such rapid synthesis,¿ Erie observed, ¿is believed to be essential for proper cellular function. The discovery of this additional allosteric [bacterial enzyme] site will dramatically change the view of how transcription is regulated in cells.
¿Many cancers,¿ Erie went on, ¿involve overexpression or improper expression of genes, and some are regulated at the level of transcription. To understand how these illnesses occur, we have to understand the details of RNA polymerase, which people have been studying for 40 years. Knowing now,¿ she concluded, ¿that there are two binding sites on the enzyme instead of one will enable scientists to interpret data they collect much more accurately.¿