Primary structure of NuMA, an intranuclear protein that defines a novel pathway for segregation of proteins at mitosis.
From a collection of monoclonal antibodies that specifically bind to various parts of the mitotic apparatus in human cells (1991. J. Cell Biol. 112: 1083-1097), two (1F1 and 1H1) recognize a greater than 200-kD intranuclear protein that associates with the spindle immediately upon nuclear envelope breakdown and progresses down the spindle microtubules to concentrate ultimately at the pericentrosomal region. At the completion of anaphase this protein dissociates from the spindle microtubules and is imported into the regenerating nuclei through the nuclear pores. Overlapping cDNA clones that span the entire length of the corresponding 7.2-kb mRNA reveal an encoded polypeptide of 236,278 D that is predicted to contain two globular domains separated by a discontinuous alpha-helix with characteristics for adopting a coiled-coil structure. The corresponding gene is highly conserved but neither the DNA sequence nor the predicted amino acid sequence shows significant homology to any previously reported. Since the cDNA also encodes the epitopes recognized by antibodies specific for two previously described proteins, NuMA and centrophilin, and all three show similar molecular weights and localization during the cell cycle, NuMA, centrophilin, and the 1F1/1H1 antigen represent either the same protein or a family of proteins, for which the original name, NuMA, seems most appropriate. While the function of NuMA remains uncertain, its unusual pattern of segregation at mitosis defines a novel pathway for the segregation of nuclear proteins during cell division.
Compton
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Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Szilak
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Cleveland
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D000595:Amino Acid Sequence; D034961:Antigens, Nuclear; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002503:Centromere / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009685:Nuclear Envelope / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D011487:Protein Conformation; D008941:Spindle Apparatus / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D004247:DNA