title: The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.
abstract: AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence.
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy Istituto Pasteur Fondazione Cenci Bolognetti, Rome 00185, Italy Istituto di Biologia e Patologia Molecolari CNR Roma, 00185, Italy.
authors: Romina
authors: R
authors: Burla
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy.
authors: Mariateresa
authors: M
authors: Carcuro
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy.
authors: Mattia La
authors: ML
authors: Torre
authors: Istituto Superiore di Sanità, Rome, 00185, Italy.
authors: Federica
authors: F
authors: Fratini
authors: Istituto Superiore di Sanità, Rome, 00185, Italy.
authors: Marco
authors: M
authors: Crescenzi
authors: Fondazione Policlinico Tor Vergata, Roma, 00133, Italy.
authors: Maria Rosaria
authors: MR
authors: D'Apice
authors: Dipartimento di Biomedicina e Prevenzione, Università di Roma Tor Vergata, Roma 00133, Italy.
authors: Paola
authors: P
authors: Spitalieri
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy.
authors: Grazia Daniela
authors: GD
authors: Raffa
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy.
authors: Letizia
authors: L
authors: Astrologo
authors: Istituto di Genetica Molecolare, CNR Bologna, 40136, Italy.
authors: Giovanna
authors: G
authors: Lattanzi
authors: Istituto di Biologia e Patologia Molecolari CNR Roma, 00185, Italy.
authors: Enrico
authors: E
authors: Cundari
authors: Dipartimento di Medicina Molecolare, Sapienza, Università di Roma, Rome 00185, Italy.
authors: Domenico
authors: D
authors: Raimondo
authors: Unità di Oncogenomica ed Epigenetica, Istituto Nazionale Tumori Regina Elena, Roma 00144, Italy.
authors: Annamaria
authors: A
authors: Biroccio
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy Istituto di Biologia e Patologia Molecolari CNR Roma, 00185, Italy maurizio.gatti@uniroma1.it.
authors: Maurizio
authors: M
authors: Gatti
authors: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, 00185, Italy Istituto di Biologia e Patologia Molecolari CNR Roma, 00185, Italy isabella.saggio@uniroma1.it.
authors: Isabella
authors: 0000-0002-9497-7415
authors: I
authors: Saggio
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D034921:Lamin Type B / Q000378:metabolism*; D008938:Mitosis; D009685:Nuclear Envelope / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D059505:Telomere Homeostasis
chemical_list: C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D034904:Lamin Type A; D034921:Lamin Type B
keywords: cell senescence; lamin; laminopathies; nuclear lamina; progeria; telomeres