LIM-domain proteins TRIP6 and LPP associate with shelterin to mediate telomere protection.

Aging
Samantha A Sheppard, Diego Loayza

Abstract

POT1 is the single stranded telomeric overhang binding protein, and is part of the shelterin complex, a group of six proteins essential for proper telomere function. The reduction or abrogation of POT1 DNA binding activity in mammalian cells results in telomere elongation, or activation of the ATR DNA damage response at telomeres. Therefore, overhang binding represents the functionally relevant activity of POT1. To better understand the roles of POT1, we sought to isolate proteins that interact with the DNA binding domain of the protein. A yeast two-hybrid screen was implemented using a C-terminal truncation termed POT1DeltaC, retaining the DNA binding domain. This screen yielded a partial cDNA corresponding to TRIP6, a member of the LIM domain protein family. TRIP6 could co-immunoprecipitate with POT1, TRF2 and TIN2 in human cells, arguing for association with the whole shelterin complex, and was detected at telomeres by ChIP. TRIP6 depletion by siRNA led to the induction of telomere dysfunction induced foci (TIFs), indicating a role in telomere protection. A closely related LIM domain protein, LPP, was also found at telomeres and was also important for repressing the DNA damage response. We propose that TRIP6 and LPP are both...Continue Reading

References

Jun 8, 2004·Nature Cell Biology·Dan LiuZhou Songyang
Nov 3, 2004·Nature Reviews. Molecular Cell Biology·Julie L Kadrmas, Mary C Beckerle
Sep 17, 2005·Genes & Development·Titia de Lange

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Citations

Aug 11, 2010·FEBS Letters·Marie-Josèphe Giraud-PanisEric Gilson
Oct 14, 2017·Journal of Cell Communication and Signaling·Elaine NganPeter M Siegel
Nov 8, 2011·Biology of the Cell·Semjon WillierThomas G P Grunewald
Apr 27, 2011·Cell Cycle·Samantha A SheppardDiego Loayza
Jul 9, 2011·Nucleus·Raffaella Diotti, Diego Loayza
Oct 26, 2012·Cell Cycle·Anna Bianchi-Smiraglia, Mikhail A Nikiforov
Feb 23, 2020·Cancer Cell International·Xiaohui ZhaoYan Zhang
Jul 22, 2014·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yun-Ju LaiTsu-Wei Wang

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Methods Mentioned

BETA
two-hybrid
immunoprecipitation
Gel shift
transfections
co-immunoprecipitation
immunoprecipitations
pull down
two
transfection
yeast

Software Mentioned

SlideBook

Related Concepts

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