Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 differe...Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.展开更多
Cell aging,the fundamental unit of biological decay,is responsible for senile disease. With the development of research,the mechanism of cell aging has been investigated in molecular level. Two hypotheses have emerged...Cell aging,the fundamental unit of biological decay,is responsible for senile disease. With the development of research,the mechanism of cell aging has been investigated in molecular level. Two hypotheses have emerged to explain the reason that lamins contribute to cell aging,one is the mechanical stress hypothesis,the other is the gene expression hypothesis. The latter proposes that mutations in A-type lamins lead to abnormal tissue-specific gene regulation. In recent years,the molecular mechanisms of lamins causing cell aging primarily include gene mutation,Zmpste24 mutation,CAAX mutation and other mutations. These mutations in the gene that encode nuclear lamins cause nuclear lamina damage directly and result in cell aging,which have been associated with several degenerative disorders.展开更多
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Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.
文摘Cell aging,the fundamental unit of biological decay,is responsible for senile disease. With the development of research,the mechanism of cell aging has been investigated in molecular level. Two hypotheses have emerged to explain the reason that lamins contribute to cell aging,one is the mechanical stress hypothesis,the other is the gene expression hypothesis. The latter proposes that mutations in A-type lamins lead to abnormal tissue-specific gene regulation. In recent years,the molecular mechanisms of lamins causing cell aging primarily include gene mutation,Zmpste24 mutation,CAAX mutation and other mutations. These mutations in the gene that encode nuclear lamins cause nuclear lamina damage directly and result in cell aging,which have been associated with several degenerative disorders.
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.
