• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Nontelomeric TRF2-REST interaction modulates neuronal gene silencing and fate of tumor and stem cells.

Removal of TRF2, a telomere shelterin protein, recapitulates key aspects of telomere attrition including the DNA-damage response and cell-cycle arrest [1]. Distinct from the response of proliferating cells to loss of TRF2 [2, 3], in rodent noncycling cells, TRF2 inhibition promotes differentiation and growth [4, 5]. However, the mechanism that couples telomere gene-silencing features [6-8] to differentiation programs has yet to be elucidated. Here we describe an extratelomeric function of TRF2 in the regulation of neuronal genes mediated by the interaction of TRF2 with repressor element 1-silencing transcription factor (REST), a master repressor of gene networks devoted to neuronal functions [9-12]. TRF2-REST complexes are readily detected by coimmunoprecipitation assays and are localized to aggregated PML-nuclear bodies in undifferentiated pluripotent human NTera2 stem cells. Inhibition of TRF2, either by a dominant-negative mutant or by RNA interference, dissociates TRF2-REST complexes resulting in ubiquitin-proteasomal degradation of REST. Consequentially, REST-targeted neural genes (L1CAM, beta3-tubulin, synaptophysin, and others) are derepressed, resulting in acquisition of neuronal phenotypes. Notably, selective damage to telomeres without affecting TRF2 levels causes neither REST degradation nor cell differentiation. Thus, in addition to protecting telomeres, TRF2 possesses a novel role in stabilization of REST thereby controlling neural tumor and stem cell fate.

Pubmed ID: 18818083


  • Zhang P
  • Pazin MJ
  • Schwartz CM
  • Becker KG
  • Wersto RP
  • Dilley CM
  • Mattson MP


Current biology : CB

Publication Data

October 14, 2008

Associated Grants

  • Agency: NIA NIH HHS, Id: Z01 AG000314-07
  • Agency: NIA NIH HHS, Id: Z01 AG000317-07
  • Agency: NIA NIH HHS, Id: ZIA AG000378-02

Mesh Terms

  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Silencing
  • Humans
  • Neuroblastoma
  • Neurons
  • Pluripotent Stem Cells
  • Repressor Proteins
  • Telomeric Repeat Binding Protein 2