DNA-protein kinase catalytic subunit-interacting protein KIP binds telomerase by interacting with human telomerase reverse transcriptase

Eui Lee Gun, Young Yu Eun, Hyun Cho Chae, Junho Lee, Mark T. Muller, Kwon Chung In

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44 Citations (Scopus)

Abstract

Telomere homeostasis, a process that is essential for continued cell proliferation and genomic stability, is regulated by endogenous telomerase and a collection of associated proteins. In this paper, a protein called KIP (previously reported as a protein that binds specifically to DNA-dependent protein kinase), has been identified as a telomerase-regulating activity based on the following pieces of evidence. First, complexes between KIP and the catalytic subunit of telomerase (hTERT) were identified using the yeast two-hybrid technique. Second, antibodies specific to KIP immunoprecipitate human telomerase in cell-free extracts. Third, immunolocalization experiments demonstrate that KIP is a nuclear protein that co-localizes with hTERT in cells. Fourth, KIP binds to hTERT both in vitro and in vivo in the absence of human telomerase RNA or telomeric DNA, thus defining the catalytic subunit of telomerase as the site of physical interaction. Fifth, co-immunoprecipitation experiments suggest that KIP-hTERT complexes form readily in cells and that overexpression of KIP in telomerase-positive cells increases endogenous telomerase activity. Finally, continued overespression of KIP (60 population doublings) resulted in cells with elongated telomeres; thus, KIP directly or indirectly stimulates telomerase activity through hTERT and contributes to telomere leagthening. The collective data in this paper suggest that KIP plays a positive role in telomere length maintenance and/or regulation and may represent a novel target for anti-cancer drug development.

Original languageEnglish
Pages (from-to)34750-34755
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number33
DOIs
Publication statusPublished - 2004 Aug 13

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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