Objective:The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal ...Objective:The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal protein,termed progerin. To investigate the underlying pathogenic mechanism,we studied the nuclear co-localization and association of progerin interactive partner proteins (PIPPs) with lamina proteins. Methods:Both wild-type (WT) and progeria fibroblasts were studied by various methods including confocal microscopy,immunoprecipitation and Western blot.Results:All PIPPs discovered so-far co-localized with lamin A/C. In addition,the PIPPs were selectively associated with lamina proteins. An increased immunofluorescent staining signal was found for Mel18 in HGPS as compared to WT cells. An association of Mel18 with emerin was observed in HGPS,but not in WT cells. Conclusion:Based on these findings,we propose that PIPPs,along with associated lamina proteins may form a pathogenic progerin-containing protein complex.展开更多
文摘Objective:The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal protein,termed progerin. To investigate the underlying pathogenic mechanism,we studied the nuclear co-localization and association of progerin interactive partner proteins (PIPPs) with lamina proteins. Methods:Both wild-type (WT) and progeria fibroblasts were studied by various methods including confocal microscopy,immunoprecipitation and Western blot.Results:All PIPPs discovered so-far co-localized with lamin A/C. In addition,the PIPPs were selectively associated with lamina proteins. An increased immunofluorescent staining signal was found for Mel18 in HGPS as compared to WT cells. An association of Mel18 with emerin was observed in HGPS,but not in WT cells. Conclusion:Based on these findings,we propose that PIPPs,along with associated lamina proteins may form a pathogenic progerin-containing protein complex.
