Mutations in the nuclear lamin proteins resulting in their aberrant assembly in the cytoplasm.
We have constructed a series of mutations in the human A lamin cDNA to identify and alter the nuclear localization signal using an in vivo functional assay system. The nuclear localization signal in the lamin proteins has both structural and functional similarities with that of the SV40 large T-antigen. Mutations within this functional domain result in the assembly of cytoplasmic tubular structures, and the behavior of these mutants suggests a post-translational dimerization of the lamin proteins prior to their transport into the nucleus. In the course of this work other regions of the carboxy terminus of the A/C lamin proteins have been implicated in the proper assembly and structure of the nuclear envelope.
Loewinger
L
L
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.
McKeon
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D034882:Lamins; D008969:Molecular Sequence Data; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D034882:Lamins; D009687:Nuclear Proteins