title: Physiological Expression and Accumulation of the Products of Two Upstream Open Reading Frames mrtl and MycHex1 Along With p64 and p67 Myc From the Human c-myc Locus.
abstract: In addition to the canonical c-Myc p64 and p67 proteins, the human c-myc locus encodes two distinct proteins, mrtl (myc-related translation/localization regulatory factor) and MycHex1 (Myc Human Exon 1), from the upstream open reading frames within the 5'-untranslated region of the c-myc P0 mRNA. The aim of this study is to examine simultaneously, for the first time, mrtl, MycHex1, c-Myc p64, and p67 in human tumor cell lines and pediatric brain tumor tissues. Western blot analysis demonstrated endogenous mrtl, MycHex1, c-Myc p64, and p67 simultaneously. The relative abundance of mrtl and MycHex1 were consistent among a variety of human tumor cell lines, and the relative intensities of mrtl and MycHex1 correlated positively. Confocal imaging revealed mrtl predominantly localized to the nuclear envelope, along with prominent reticular pattern in the cytoplasm. MycHex1 was observed as a series of bright foci located within the nucleus, a subset of which colocalized with fibrillarin. mrtl and MycHex1 co-immunoprecipitated with RACK1, c-Myc, fibrillarin, coilin, and with each other. These findings suggest that mrtl and MycHex1 have multiple interaction partners in both the nucleus and cytoplasm. Sequence analyses confirmed a known polymorphism of mrtl at base 1965 (G>T) and new mutations at bases 1900 (C>G) and 1798 (C>G). Evidence is presented for expression and stable accumulation of all four proteins encoded by three distinct non-overlapping open reading frames within the human c-myc locus. Additional work is warranted to further elucidate the functional or regulatory roles of these molecules in regulation of c-Myc and in oncogenesis.
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Mi Hong
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chae-Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Jun
authors.affiliation: Department of Medicine and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Blume
authors.affiliation: Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Hyoung Soo
authors.initials: HS
authors.lastname: Choi
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D056426:Genetic Loci; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc
keywords: MycHex1; NUCLEAR LOCALIZATION; UPSTREAM OPEN READING FRAMES; c-myc GENE; mrtl