Senior Scholar Award in Aging
Olivia M. Pereira-Smith, Ph.D.
University of Texas Health Science Center - San Antonio

The Role of the MORF/MRG Family of Novel Transcription Factors in In Vitro and In Vivo Aging

Normal cells grown in culture have a limited potential to divide and eventually become terminally non-dividing. This is called cell or replicative senescence and is used as a model to study aging at the cell level. Tumor-derived cells, in contrast, divide constantly without control. We have found that tumor cells grow as they do because they have disrupted the genes involved in cell senescence and that they can be made to stop dividing by re-expression of these genes. We have cloned one of these genes and named it MORF4 (Mortality Factor on Human Chromosome 4). MORF4 is a member of a novel gene family, MRG15 and MRGX (MORF related genes), that functions to control expression of other genes involved in cell growth and cell division. We want to determine the mechanism by which MORF4 causes tumor cells to stop dividing, as this could provide potential therapies for certain tumors. The approach we propose to take is to introduce the gene into two tumor cell lines, one that is affected by MORF4 and one that is not. We will then analyze protein complexes in the nucleus and cytoplasm of the cells to determine any changes that result from over expression of MORF4, particularly in the tumor cells that stop dividing after the introduction of MORF4. We will also analyze wild-type and MRG15 null embryos for differences in gene expression which will allow us to identify the target genes for action by MRG15. This will help in our understanding of the function of MRG15 and in turn the function of MORF4.

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