The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

被引:26
作者
Burla, Romina [1 ,2 ,3 ]
Carcuro, Mariateresa [1 ]
La Torre, Mattia [1 ]
Fratini, Federica [4 ]
Crescenzi, Marco [4 ]
D'Apice, Maria Rosaria [5 ]
Spitalieri, Paola [6 ]
Raffa, Grazia Daniela [1 ]
Astrologo, Letizia [1 ]
Lattanzi, Giovanna [7 ]
Cundari, Enrico [3 ]
Raimondo, Domenico [8 ]
Biroccio, Annamaria [9 ]
Gatti, Maurizio [1 ,3 ]
Saggio, Isabella [1 ,3 ]
机构
[1] Univ Roma La Sapienza, Dipartimento Biol & Biotecnol C Darwin, I-00185 Rome, Italy
[2] Fdn Cenci Bolognetti, Ist Pasteur, I-00185 Rome, Italy
[3] CNR Roma, Ist Biol & Patol Mol, I-00185 Rome, Italy
[4] Ist Super Sanita, I-00185 Rome, Italy
[5] Fdn Policlin Tor Vergata, I-00133 Rome, Italy
[6] Univ Roma Tor Vergata, Dipartimento Biomed & Prevenz, I-00133 Rome, Italy
[7] CNR Bologna, Ist Genet Mol, I-40136 Bologna, Italy
[8] Univ Roma La Sapienza, Dipartimento Med Mol, I-00185 Rome, Italy
[9] Ist Nazl Tumori Regina Elena, Unita Oncogen & Epigenet, I-00144 Rome, Italy
关键词
lamin; telomeres; laminopathies; progeria; nuclear lamina; cell senescence; HUTCHINSON-GILFORD PROGERIA; A-TYPE LAMINS; MANDIBULOACRAL DYSPLASIA; NUCLEAR-ENVELOPE; CHROMATIN ORGANIZATION; HUMAN-CELLS; IN-VIVO; PRELAMIN; EXPRESSION; UBIQUITIN;
D O I
10.1098/rsob.160103
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:11
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