Progerin is a truncated version of lamin A protein involved in Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a silent point mutation (C1824T) in the lamin A gene, LMNA. 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 Hutchinson–Gilford progeria syndrome cases are heterozygous for this silent point mutation 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. In Hutchinson-Gilford Progeria Syndrome cells, progerin increases the frequency of unrepaired double-strand breaks in DNA following exposure to ionizing radiation. This finding suggests that the lamin A-associated nuclear membrane has an important role in repair of DNA double-strand breaks.
Recently, rapamycin has been shown to prevent progerin aggregates in cells and hence delay premature aging.
- Eriksson M, Brown WT, Gordon LB, et al. (May 2003). "Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome". Nature. 423 (6937): 293–8. doi:10.1038/nature01629. PMID 12714972.
- McClintock D, Gordon LB, Djabali K (February 2006). "Hutchinson–Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody". Proc. Natl. Acad. Sci. U.S.A. 103 (7): 2154–9. doi:10.1073/pnas.0511133103. PMC . PMID 16461887.
- "Anti-cancer Drugs May Hold Promise For Premature Aging Disorder". Retrieved 2008-07-15.
- Scaffidi P, Misteli T (April 2008). "Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing". Nat. Cell Biol. 10 (4): 452–9. doi:10.1038/ncb1708. PMC . PMID 18311132.
"Adult stem cell changes underlie rare genetic disease associated with accelerated aging". Retrieved 2008-07-15.
- Noda A, Mishima S, Hirai Y, Hamasaki K, Landes RD, Mitani H, Haga K, Kiyono T, Nakamura N, Kodama Y (2015). "Progerin, the protein responsible for the Hutchinson-Gilford progeria syndrome, increases the unrepaired DNA damages following exposure to ionizing radiation". Genes Environ. 37: 13. doi:10.1186/s41021-015-0018-4. PMC . PMID 27350809.
- Liu B, Zhou Z (June 2008). "Lamin A/C, laminopathies and premature ageing". Histol. Histopathol. 23 (6): 747–63. PMID 18366013.
|This protein-related article is a stub. You can help Wikipedia by expanding it.|