New Insights into the Role of Progerin in Cellular Pathology

Significance The focus of research on the cause of HGPS has been the permanent farnesylation of progerin. In contrast, little attention has been given to how the deletion of residues 607-656, which are located just upstream of the CAAX box, may also affect other LA functions and potentially influence the phenotypes of HGPS. The studies described in this proposal aim to identify how regulatory modifications in wild type LA that are missing in progerin influence the structure and dynamics of the nuclear lamin networks in both the lamina and the nucleoplasm. This work could potentially identify new therapeutic targets to diminish the damaging effects of progerin on cells that lead to HGPS.