Abstract
Mutations in the LMNA gene are associated with a spectrum of human dystrophic diseases termed the "nuclear laminopathies." We recently found that the accumulation of the inner nuclear envelope proteins SUN1 is pathogenic in progeric and dystrophic laminopathies. This conclusion arose from the unexpected observation that the deletion of Sun1, instead of accelerating aging, actually ameliorated the progeric and dystrophic phenotypes in Lmna-deficient mice. In human cells, knocking down SUN1 corrected the nuclear aberrancies and the senescent tendencies of HGPS (Hutchinson-Gilford progeria syndrome) skin fibroblasts. Here we offer additional comments on the contributions of SUN1 and the process of normal protein turnover to cellular aging.
Publication types
-
Research Support, N.I.H., Intramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cellular Senescence
-
Humans
-
Lamin Type A / deficiency
-
Lamin Type A / genetics
-
Lamin Type A / metabolism
-
Membrane Proteins / antagonists & inhibitors
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Mice, Knockout
-
Microtubule-Associated Proteins / antagonists & inhibitors
-
Microtubule-Associated Proteins / genetics
-
Microtubule-Associated Proteins / metabolism*
-
Nuclear Envelope / metabolism
-
Nuclear Matrix / metabolism
-
Nuclear Proteins / antagonists & inhibitors
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism*
-
Progeria / metabolism*
-
Progeria / pathology
Substances
-
Lamin Type A
-
Membrane Proteins
-
Microtubule-Associated Proteins
-
Nuclear Proteins
-
SUN1 protein, human