title: Subcellular localization of antizyme inhibitor 2 in mammalian cells: Influence of intrinsic sequences and interaction with antizymes.
abstract: Ornithine decarboxylase (ODC) and the antizyme inhibitors (AZIN1 and AZIN2), regulatory proteins of polyamine levels, are antizyme-binding proteins. Although it is widely recognized that ODC is mainly a cytosolic enzyme, less is known about the subcellular distribution of AZIN1 and AZIN2. We found that these proteins, which share a high degree of homology in their amino acid sequences, presented differences in their subcellular location in transfected mammalian cells. Whereas ODC was mainly present in the cytosol, and AZIN1 was found predominantly in the nucleus, interestingly, AZIN2 was located in the ER-Golgi intermediate compartment (ERGIC) and in the cis-Golgi network, apparently not related to any known cell-sorting sequence. Our results rather suggest that the N-terminal region may be responsible for this particular location, since its deletion abrogated the incorporation of the mutated AZIN2 to the ERGIC complex and, on the other hand, the substitution of this sequence for the corresponding sequence in ODC, translocated ODC from cytosol to the ERGIC compartment. Furthermore, the coexpression of AZIN2 with any members of the antizyme family induced a shift of AZIN2 from the ERGIC to the cytosol. These findings underline the complexity of the AZs/AZINs regulatory system, supporting early evidence that relates these proteins with additional functions other than regulating polyamine homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology B and Immunology, University of Murcia, Spain.
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: López-Contreras
authors.forename: Berta L
authors.initials: BL
authors.lastname: Sánchez-Laorden
authors.forename: Bruno
authors.initials: B
authors.lastname: Ramos-Molina
authors.forename: María E
authors.initials: ME
authors.lastname: de la Morena
authors.forename: Asunción
authors.initials: A
authors.lastname: Cremades
authors.forename: Rafael
authors.initials: R
authors.lastname: Peñafiel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry; D004721:Endoplasmic Reticulum; D004791:Enzyme Inhibitors; D006056:Golgi Apparatus; D006801:Humans; D051379:Mice; D009955:Ornithine Decarboxylase / Q000032:analysis; D021381:Protein Transport; D011506:Proteins / Q000032:analysis*; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase