Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation

Kyung Kim Mi, Ran Kang Mi, Wook Nam Hyung, Young Seuk Bae, Sam Kim Yu, In Kwon Chung

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Telomere maintenance is essential for continued cell proliferation and chromosome stability. Telomeres are maintained by telomerase and a collection of associated proteins. The telomeric protein telomeric repeat binding factor 1 (TRF1) negatively regulates telomere length by inhibiting access of telomerase at telomere termini. Here we report that TRF1 interacts with the βsubunit of casein kinase 2 (CK2) and serves as a substrate for CK2. CK2-mediated phosphorylation is required for the efficient telomere binding of TRF1 in vitro and in vivo. Inhibition of CK2 by the CK2 inhibitor 5,6-dichloro-1-β-D- ribofuranosyl-benzimidazole decreased the ability of TRF1 to bind telomeric DNA. The resulting telomere-unbound form of TRF1 was then ubiquitinated and degraded by the proteasome. Partial knock-down of CK2 by small interfering RNA resulted in removal of TRF1 from telomeres and subsequent degradation of TRF1. Mapping of the CK2 target site identified threonine 122 as a substrate in TRF1. Athreonine to alanine change at this position led to a diminished DNA binding due to reduced dimerization of TRF1. In addition, phosphorylation of threonine 122 seemed critical for TRF1-mediated telomere length control. Our findings suggest that CK2-mediated phosphorylation of TRF1 plays an important role in modulating telomere length homeostasis by determining the levels of TRF1 at telomeres.

Original languageEnglish
Pages (from-to)14144-14152
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number20
DOIs
Publication statusPublished - 2008 May 16

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Casein Kinase II
Phosphorylation
Telomere
Telomerase
Threonine
Telomeric Repeat Binding Protein 1
Telomere-Binding Proteins
Telomere Homeostasis
Chromosomal Instability
Dimerization
DNA
Cell proliferation
Proteasome Endopeptidase Complex
Substrates
Chromosomes
Alanine
Small Interfering RNA
Proteins
Maintenance
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mi, Kyung Kim ; Mi, Ran Kang ; Hyung, Wook Nam ; Bae, Young Seuk ; Yu, Sam Kim ; Chung, In Kwon. / Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 20. pp. 14144-14152.
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Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. / Mi, Kyung Kim; Mi, Ran Kang; Hyung, Wook Nam; Bae, Young Seuk; Yu, Sam Kim; Chung, In Kwon.

In: Journal of Biological Chemistry, Vol. 283, No. 20, 16.05.2008, p. 14144-14152.

Research output: Contribution to journalArticle

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