Progerin (P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a single nucleotide polymorphism (C1824T) in the gene that codes for Lamin A. This mutation activates a cryptic splice site and gives rise to a form of lamin A with a deletion of 50 amino acids near the C-terminus. Approximately 80% of all Hutchinson–Gilford progeria syndrome cases are heterozygous for this deleterious single nucleotide polymorphism within exon 11 of the LMNA gene.
Lamin A constitutes a major structural component of the lamina, a scaffold of proteins found inside the nuclear membrane of a cell; progerin does not properly integrate into the lamina, which disrupts the scaffold structure and leads to significant disfigurement of the nucleus, characterized by a lobular shape. Progerin activates genes that regulate stem cell differentiation via the Notch signaling pathway. Progerin increases the frequency of unrepaired double-strand breaks in DNA following exposure to ionizing radiation. This finding suggests that the nuclear lamina has an important role in the repair of DNA double-strand breaks.
Recently, rapamycin has been shown to prevent progerin aggregates in cells and hence delay premature aging.
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