Presentation description

Polyamines are polycationic molecules that are found in all living organisms. The three most abundant are putrescine, spermidine, and spermine. Their positively charged structure allows them to interact with many negatively charged molecules such as DNA, RNA, and proteins. These interactions provide them with essential roles in transcription, translation, cell growth, and other essential processes in the cell. Polyamines are relevant for cancer research since numerous cancer types have been shown to contain an increased concentration of polyamines that allow the cells to grow and proliferate. Understanding the regulation of the enzymes that synthesize and catabolize polyamines will uncover how the cell senses and regulates their levels. We are interested in the regulation of adenosylmethionine decarboxylase 1 (AMD1) which is overexpressed in prostate and breast cancer, and for its relevance in spermidine and spermine synthesis. AMD1's function is to decarboxylase adenosylmethionine to provide spermidine synthase (SRM) and spermine synthase (SMS) an aminopropyl group to synthesize spermidine or spermine respectively. Additionally, ornithine decarboxylase 1 (ODC1), an enzyme that decarboxylases ornithine is also essential to polyamine levels as it directly synthesizes putrescine. AMD1 and ODC1 are short-lived proteins that are part of rate-limiting step reactions. In this project, we generated overexpression and knock-out cell lines of polyamine enzymes to uncover the regulation of these proteins at the transcriptional and post-translational levels.