Home LiteratureArticle Details
PMID: 12782650 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres.

Genes & development ·Vol. 17 ·No. 11 ·2003-06-01 ·Pages 1328-33

Chang W, Dynek JN, Smith S

Abstract

Mammalian telomeres are coated by the sequence-specific, DNA-binding protein, TRF1, a negative regulator of telomere length. Previous results showed that ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and promoted telomere elongation. We now show that loss of TRF1 from telomeres results in ubiquitination and degradation of TRF1 by the proteasome and that degradation is required to keep TRF1 off telomeres. Ubiquitination of TRF1 is regulated by its telomere-binding status; only the telomere-unbound form of TRF1 is ubiquitinated. Our findings suggest a novel mechanism of sequential post translational modification of TRF1 (ADP-ribosylation and ubiquitination) for regulating access of telomerase to telomeres.

MeSH Terms
Adenosine Diphosphate Ribose/metabolism Animals Base Sequence Cloning, Molecular Endopeptidases/metabolism Mammals Recombinant Proteins/metabolism Telomere/genetics Telomeric Repeat Binding Protein 1/genetics,metabolism Ubiquitin/metabolism
Chemicals
Recombinant Proteins Telomeric Repeat Binding Protein 1 Ubiquitin Adenosine Diphosphate Ribose Endopeptidases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chang William
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
Dynek Jasmin N
Smith Susan
References (29)
29 references, click to expand
  1. Fission yeast F-box protein Pof3 is required for genome integrity and telomere function.
    Mol Biol Cell. 2002 Jan;13(1):211-24 PMID: 11809834
  2. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2.
    Nat Genet. 1997 Oct;17(2):231-5 PMID: 9326950
  3. Senescence induced by altered telomere state, not telomere loss.
    Science. 2002 Mar 29;295(5564):2446-9 PMID: 11923537
  4. The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein (TAB182).
    J Biol Chem. 2002 Apr 19;277(16):14116-26 PMID: 11854288
  5. Targeting assay to study the cis functions of human telomeric proteins: evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2.
    Mol Cell Biol. 2002 May;22(10):3474-87 PMID: 11971978
  6. Functional characterization of the poly(ADP-ribose) polymerase activity of tankyrase 1, a potential regulator of telomere length.
    J Mol Biol. 2002 Oct 18;323(2):217-24 PMID: 12381316
  7. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
    Cell. 1985 Dec;43(2 Pt 1):405-13 PMID: 3907856
  8. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
    EMBO J. 1992 May;11(5):1921-9 PMID: 1582420
  9. Telomeric localization of TRF2, a novel human telobox protein.
    Nat Genet. 1997 Oct;17(2):236-9 PMID: 9326951
  10. TRF2 protects human telomeres from end-to-end fusions.
    Cell. 1998 Feb 6;92(3):401-13 PMID: 9476899
  11. The ubiquitin system.
    Annu Rev Biochem. 1998;67:425-79 PMID: 9759494
  12. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.
    Science. 1998 Nov 20;282(5393):1484-7 PMID: 9822378
  13. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14723-8 PMID: 9843956
  14. Mammalian telomeres end in a large duplex loop.
    Cell. 1999 May 14;97(4):503-14 PMID: 10338214
  15. Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes.
    J Cell Sci. 1999 Nov;112 ( Pt 21):3649-56 PMID: 10523501
  16. Positive and negative regulation of telomerase access to the telomere.
    J Cell Sci. 2000 Oct;113 Pt 19:3357-64 PMID: 10984427
  17. Tankyrase promotes telomere elongation in human cells.
    Curr Biol. 2000 Oct 19;10(20):1299-302 PMID: 11069113
  18. The F-box protein family.
    Genome Biol. 2000;1(5):REVIEWS3002 PMID: 11178263
  19. The world according to PARP.
    Trends Biochem Sci. 2001 Mar;26(3):174-9 PMID: 11246023
  20. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism.
    Exp Cell Res. 2001 Aug 1;268(1):7-13 PMID: 11461113
  21. Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2.
    Mol Cell. 2001 Aug;8(2):351-61 PMID: 11545737
  22. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres.
    Mol Cell Biol. 2002 Jan;22(1):332-42 PMID: 11739745
  23. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain.
    Cell. 1994 Sep 9;78(5):787-98 PMID: 8087846
  24. Specific association of human telomerase activity with immortal cells and cancer.
    Science. 1994 Dec 23;266(5193):2011-5 PMID: 7605428
  25. A human telomeric protein.
    Science. 1995 Dec 8;270(5242):1663-7 PMID: 7502076
  26. Control of telomere length by the human telomeric protein TRF1.
    Nature. 1997 Feb 20;385(6618):740-3 PMID: 9034193
  27. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
    Cell. 1997 Mar 7;88(5):593-602 PMID: 9054499
  28. UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior.
    Genes Dev. 1997 Apr 1;11(7):863-75 PMID: 9106658
  29. Protection of mammalian telomeres.
    Oncogene. 2002 Jan 21;21(4):532-40 PMID: 11850778
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1077103
Published
2003-06-01
Pages
1328-33
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196064
Subset
IM
Grants
NCI NIH HHS · R01 CA095099 · United States
NCI NIH HHS · R01 CA95099-01 · United States
External Links
PubMed source DOI: 10.1101/gad.1077103 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2