title: PTTG1/securin modulates microtubule nucleation and cell migration.
abstract: Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference-mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Científicas, 41092 Seville, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Moreno-Mateos
authors.forename: Águeda G
authors.initials: ÁG
authors.lastname: Espina
authors.forename: Belén
authors.initials: B
authors.lastname: Torres
authors.forename: María M
authors.initials: MM
authors.lastname: Gámez del Estal
authors.forename: Ana
authors.initials: A
authors.lastname: Romero-Franco
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ríos
authors.forename: José A
authors.initials: JA
authors.lastname: Pintor-Toro
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D018385:Centrosome; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D064249:Securin; D014404:Tubulin / Q000378:metabolism; D014945:Wound Healing
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D003598:Cytoskeletal Proteins; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D064249:Securin; D014404:Tubulin; C578002:pituitary tumor-transforming protein 1, human