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

Open Biol. 2016 Aug;6(8):160103. doi: 10.1098/rsob.160103.

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.

Keywords: cell senescence; lamin; laminopathies; nuclear lamina; progeria; telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Cells, Cultured
  • Cellular Senescence
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Lamin Type A / metabolism*
  • Lamin Type B / metabolism*
  • Mitosis
  • Nuclear Envelope / metabolism
  • Telomere / metabolism
  • Telomere Homeostasis

Substances

  • AKTIP protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Lamin Type A
  • Lamin Type B