A novel form of the telomere-associated protein TIN2 localizes to the nuclear matrix.
Telomeres are specialized heterochromatin at the ends of linear chromosomes. Telomeres are crucial for maintaining genome stability and play important roles in cellular senescence and tumor biology. Six core proteins-TRF1, TRF2, TIN2, POT1, TPP1 and Rap1 (termed the telosome or shelterin complex)-regulate telomere structure and function. One of these proteins, TIN2, regulates telomere length and structure indirectly by interacting with TRF1, TRF2 and TPP1, but no direct function has been attributed to TIN2. Here we present evidence for a TIN2 isoform (TIN2L) that differs from the originally described TIN2 isoform (TIN2S) in two ways: TIN2L contains an additional 97 amino acids, and TIN2L associates strongly with the nuclear matrix. Stringent salt and detergent conditions failed to extract TIN2L from the nuclear matrix, despite removing other telomere components, including TIN2S. In human mammary epithelial cells, each isoform showed a distinct nuclear distribution both as a function of cell cycle position and telomere length. Our results suggest a dual role for TIN2 in mediating the function of the shelterin complex and tethering telomeres to the nuclear matrix.
Kaminker
Patrick G
PG
Buck Institute for Age Research, Novato, California, USA.
Kim
Sahn-Ho
SH
Desprez
Pierre-Yves
PY
Campisi
Judith
J
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D015530:Nuclear Matrix / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C495876:ACD protein, human; D020033:Protein Isoforms; D000089804:Shelterin Complex; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins