Novel Protein Discovery Provides Vital Clue to Cancer /

CAUTION - ADVANCE FOR AYEMS FRIDAY, APRIL 23 ADVANCE/OKLAHOMA CITY (ots-PRNewswire) - Scientists at theOklahoma Medical Research Foundation, whose previous research onthe tumor- suppressing von Hippel-Lindau gene was hailed as a"coup for cancer research" by the journal "Science", have nowlinked their discoveries to a general mechanism for controllingcell growth. Defects in the von Hippel-Lindau gene are associatedwith most cases of clear-cell renal carcinoma, the most commonform of kidney cancer, and with von Hippel-Lindau disease, a raregenetic condition that predisposes affected people to a varietyof cancers and to tumors of the eye, brain, spinal cord,pancreas, liver or adrenal gland. In two research papers published today in "Science", Drs. Joanand Ronald Conaway of OMRF's Program in Molecular and CellBiology and an interdisciplinary team of scientists includingDrs. Takumi Kamura and Michael Conrad of OMRF, Drs. Wade Harperand Stephen Elledge and their colleagues at Baylor College ofMedicine, and Dr. William Kaelin and colleagues of the Dana-Farber Cancer Institute at Harvard Medical School, reporteddiscovery of a new protein, Rbx1, that is a part of the vonHippel-Lindau, or VHL, tumor suppressor machinery. Remarkably,Rbx1 is also found as a critical component of the machinery thatcontrols cell growth and division by targeting importantregulatory proteins for destruction. "An exciting hypothesis is that, in its normal form, VHL workstogether with Rbx1 to prevent the cell from accumulating proteinsthat trigger uncontrolled cell proliferation. But a mutation inthe gene that produces VHL can cause cancer by interfering withthe cell's ability to destroy the trigger proteins, leading torunaway cell growth," said Joan Conaway, Howard Hughes MedicalInstitute investigator at OMRF. Notes Ron Conaway, "Not surprisingly, the mechanisms thatregulate protein destruction are turning out to be every bit ascomplicated and every bit as important as those that regulateprotein synthesis. The discovery of the link between VHL, Rbx1,and the protein destruction machinery should help researchersidentify the specific trigger proteins targeted by VHL and maylead to new approaches to cancer prevention and treatment." In 1993 the Conaways discovered and isolated the Elongins asproteins that help to control the mechanism that turns genes,including cancer genes, on or off. In 1995 they collaborated withDrs. Richard Klausner and Marston Linehan of the NationalInstitutes of Health (NIH) to demonstrate that the Elonginsfunction in cells with the VHL tumor suppressor protein toprevent cancer. "These findings represent a significant advance in ourunderstanding of the function of the VHL gene and how damage tothis gene leads to the manifestations in patients that we know ofas cancer," said W. Marston Linehan, M.D., Chief of the UrologicOncology Branch at the National Cancer Institute. "We stronglyfeel that it is work such as this that will one day play a majorrole in the development of effective forms of therapy forpatients with kidney cancer." The Conaways have been involved in basic biomedical researchon gene expession since the mid-1980s, when they were at the DNAXResearch Institute and Stanford University School of Medicine. In1997, the couple received the Amgen Award from the AmericanSociety of Biochemistry and Molecular Biology, a prestigiousaward reserved for young investigators who have "had significantachievements in the application of biochemistry and molecularbiology to the understanding of disease." "Joan and Ron Conaway's young careers have been marked bygreat promise resulting in major scientific contributions," saidJ. Donald Capra, M.D., OMRF president. "It is also a great sourceof pride that Joan Conaway is a Howard Hughes Medical Instituteinvestigator, one of only two in the state of Oklahoma, both ofwhom are at OMRF." The Conaways' research is supported by the Howard HughesMedical Institute, the National Institutes of Health, and byfunds provided to OMRF by the H.A. and Mary K. Chapman CharitableTrust of Tulsa, OK. ots Original Text Service: Oklahoma MedicalResearch Center Internet: http://www.newsaktuell.de Contact: PamMauldin of Oklahoma Medical Research Center, 405-271-7159 oremail, pam-mauldin@omrf.ouhsc.edu

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