Involvement of prelamin A in laminopathies.
The precursor protein of the nuclear lamina constituent lamin A is a 74-kDa protein called prelamin A which undergoes subsequent steps of posttranslational modification at its C-terminal CaaX residue. The unexpected finding that accumulation of unprocessable prelamin A is the molecular basis of the most severe laminopathies so far identified, including Hutchinson-Gilford progeria and restrictive dermopathy, has opened new perspectives in the study of the pathogenic mechanisms causing all lamin A/C-linked disorders, as well as new interest in the analysis of molecular mechanisms regulating prelamin A processing. However, complete knowledge of the cellular pathways affected downstream of prelamin A accumulation is still lacking, but it could give new insights both in normal and pathogenic mechanisms regulated by lamins. In this article, we review the involvement of defects of prelamin A processing in the pathogenesis of a group of laminopathies. In particular, we discuss the possibility that mutations leading to accumulation of particular forms of prelamin A result in specific nuclear abnormalities and impairment of nuclear functions leading to cell senescence or altered metabolism.
Maraldi
N M
NM
Laboratory of Cell Biology, Istituto Ortopedico Rizzoli, Bologna, Italy. maraldi@area.bo.cnr.it
Lattanzi
G
G
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D034904:Lamin Type A; D007797:Laminin / Q000502:physiology*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational
D034904:Lamin Type A; D007797:Laminin; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A