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P&S Journal

P&S Journal: Spring 1995, Vol.15, No.2
Research & Reports
Researchers Find Clues Close to Home

It's not often that research scientists find answers close to home. But Dr. Stephen Goff, the Higgins Professor of Biochemistry and Molecular Biophysics and a Howard Hughes Medical Institute investigator, has identified a human protein that interacts with HIV and is related to a yeast protein his wife, Dr. Marian Carlson, professor of genetics and development, has studied for 10 years. It's an odd coincidence for two scientists who have worked in the same place for 12 years but rarely have crossed professional paths.

His research findings were published in a December issue of Science.

Dr. Goff has studied HIV and other retroviruses since the 1970s. About a year and a half ago, he started looking for human factors inside the nucleus of cells that HIV might need for its life cycle. A new molecular biological technique, called the two-hybrid system, has made the search for host factors easier by allowing scientists to find unknown proteins that interact with a protein of the researcher's choice-HIV integrase protein in this case. Proteins perform structural and enzymatic functions inside viruses and cells.

Dr. Goff identified a human protein, called INI-1, that seems to help HIV integrate itself into host genetic material. New drugs to fight HIV and improvements in gene therapy may result from a better understanding of the INI-1-viral interaction. The research also provides a better understanding of how genes act in cells.

INI-1 is evolutionarily related to SNF5, the yeast protein Dr. Carlson has studied for more than 10 years as she has investigated yeast proteins responsible for transcription, a process that turns genes on and off. Yeast serves as a model system because it provides clues about what happens in transcription in higher organisms. The genetic manipulation needed to understand these biochemical pathways cannot be done in humans, but the proteins doing the job in yeast have been found to be remarkably similar to those in humans.

The protein Dr. Carlson studies is part of a complex of 10 to 12 proteins used by yeast to help genes know when they should be active. Many of these proteins, except for SNF5, have been shown to be related to proteins also used by mammals in their gene transcription. For years, scientists have known HIV and other retroviruses integrate into active regions of the human chromosome but had no way of explaining it. It is possible that INI-1 may act as a flag for the virus to find active parts of the genome where it can integrate.

copyright ©, Columbia-Presbyterian Medical Center

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