title: Identification of the human c-myc protein nuclear translocation signal.
abstract: We identified and characterized two regions of the human c-myc protein that target proteins into the nucleus. Using mutant c-myc proteins and proteins that fuse portions of c-myc to chicken muscle pyruvate kinase, we found that residues 320 to 328 (PAAKRVKLD; peptide M1) induced complete nuclear localization, and their removal from c-myc resulted in mutant proteins that distributed in both the nucleus and cytoplasm but retained rat embryo cell cotransforming activity. Residues 364 to 374 (RQRRNELKRSP; peptide M2) induced only partial nuclear targeting, and their removal from c-myc resulted in mutant proteins that remained nuclear but were cotransformationally inactive. We conjugated synthetic peptides containing M1 or M2 to human serum albumin and microinjected the conjugate into the cytoplasm of Vero cells. The peptide containing M1 caused rapid and complete nuclear accumulation, whereas that containing M2 caused slower and only partial nuclear localization. Thus, M1 functions as the nuclear localization signal of c-myc, and M2 serves some other and essential function.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: C V
authors.initials: CV
authors.lastname: Dang
authors.forename: W M
authors.initials: WM
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005455:Fluorescent Antibody Technique; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011770:Pyruvate Kinase / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D011770:Pyruvate Kinase