Reversal of laminopathies: the curious case of SUN1.
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.
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan. ychi@nhri.org.tw
Ya-Hui
YH
Chi
Chia-Yen
CY
Chen
Kuan-Teh
KT
Jeang
D000818:Animals; D016922:Cellular Senescence; D006801:Humans; D034904:Lamin Type A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D015530:Nuclear Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011371:Progeria / Q000378:metabolism* / Q000473:pathology
D034904:Lamin Type A; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C506117:SUN1 protein, human