International Research Fellowship Program: Molecular Mechanism Mediating Transcriptional Repression of the INK4a/ARF Locus by Bmi-1

Gonzalo, Susana, St. Louis MO

Investigators

Abstract

0202699 Gonzalo The International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twenty-four month research fellowship by Dr. Susana Gonzalo to work with Dr. Manuel Serrano at the National Center of Biotechnology in Madrid, Spain. For this project, the PI will identify the cis-activity promoter elements of the INK4a/ARF locus that are responsive to the transcriptional repressor Bmi-1, and then identify the transacting transcription factors that mediate Bmi-1 repression of this gene. The INK4a/ARF locus encodes two proteins (p16in4a/ARF) that are important for two different tumor suppressor pathways in mammalian cells. The expression of both of these proteins is repressed during normal cell growth, but becomes elevated in response to oncogenic stresses to prevent the proliferation and survival of cells in which an oncogene has become activated. This study is critical to understand the control mechanisms that cells use to fight cancer. Dr. Serrano is an authority in the fields of cell-cycle and tumor suppression. His lab has critical tools necessary to develop this project.