Grant: Travel Awards - Institute Community Support

Prior to cell division, the cell needs to duplicate its DNA, proteins and organelles so that the cell can partition evenly when it divides. Gene expression is controlled by regions on the DNA called promoters. Binding of certain proteins to DNA promoters can initiate the transcription of that gene to form RNA. Before this can occur, DNA must unravel from tightly bound histones, specialized proteins which keep the DNA compact and inaccessible to the transcription machinery. Histones are conserved proteins with specific chemical modifications on their amino acids tails. These modifications regulate DNA transcription by determining how tightly DNA is bound to the histones. After the RNA is synthesized from DNA, ribosomes are necessary to translate the RNA into protein. Matrix metalloproteinase 2 (MMP-2) is an enzyme with specialized roles in cutting other proteins inside and outside of cells. Inside cells, MMP-2 can be found in the nucleus, but its biological role there is unknown. We found that MMP-2 is enriched in the promoter region of the gene for making ribosomal proteins. We also found that MMP-2 can cut histones so that the DNA is more accessible for transcription. The involvement of MMP-2 in RNA ribosomal gene expression is an important new mechanism how intracellular MMP-2 may regulate cell function in the nucleus. This has major implications in cell division, particularly in rapidly dividing cells like cancer cells, whose growth rates were impaired by drugs which block MMP activity. This understanding may aid in the development of more selective MMP inhibitors for use as anticancer drugs.