PML-IV functions as a negative regulator of telomerase by interacting with TERT

Wonkyung Oh, Jaewang Ghim, Eun Woo Lee, Mi Ran Yang, Eui Tae Kim, Jin Hyun Ahn, Jaewhan Song

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Maintaining proper telomere length requires the presence of the telomerase enzyme. Here we show that telomerase reverse transcriptase (TERT), a catalytic component of telomerase, is recruited to promyelocytic leukemia (PML) nuclear bodies through its interaction with PML-IV. Treatment of interferon-α (IFNα) in H1299 cells resulted in the increase of PML proteins with a concurrent decrease of telomerase activity, as previously reported. PML depletion, however, stimulated telomerase activity that had been inhibited by IFNα with no changes in TERT mRNA levels. Upon treatment with IFNα, exogenous TERT localized to PML nuclear bodies and binding between TERT and PML increased. Immunoprecipitation and immunofluorescence analyses showed that TERT specifically bound to PML-IV. Residues 553-633 of the C-terminal region of PML-IV were required for its interaction with the TERT region spanning residues 1-350 and 595-946. The expression of PML-IV and its deletion mutant, 553-633, suppressed intrinsic telomerase activity in H1299. TERT-mediated immunoprecipitation of PML or the 553-633 fragment demonstrated that these interactions inhibited telomerase activity. H1299 cell lines stably expressing PML-IV displayed decreased telomerase activity with no change of TERT mRNA levels. Accordingly, telomere length of PML-IV stable cell lines was shortened. These results indicate that PML-IV is a negative regulator of telomerase in the post-translational state.

Original languageEnglish
Pages (from-to)2613-2622
Number of pages10
JournalJournal of cell science
Volume122
Issue number15
DOIs
Publication statusPublished - 2009 Aug 1

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Telomerase
Leukemia
Interferons
Telomere
Immunoprecipitation
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Oh, Wonkyung ; Ghim, Jaewang ; Lee, Eun Woo ; Yang, Mi Ran ; Kim, Eui Tae ; Ahn, Jin Hyun ; Song, Jaewhan. / PML-IV functions as a negative regulator of telomerase by interacting with TERT. In: Journal of cell science. 2009 ; Vol. 122, No. 15. pp. 2613-2622.
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PML-IV functions as a negative regulator of telomerase by interacting with TERT. / Oh, Wonkyung; Ghim, Jaewang; Lee, Eun Woo; Yang, Mi Ran; Kim, Eui Tae; Ahn, Jin Hyun; Song, Jaewhan.

In: Journal of cell science, Vol. 122, No. 15, 01.08.2009, p. 2613-2622.

Research output: Contribution to journalArticle

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AU - Oh, Wonkyung

AU - Ghim, Jaewang

AU - Lee, Eun Woo

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AU - Ahn, Jin Hyun

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