Home LiteratureArticle Details
PMID: 9122175 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of E2F through ubiquitin-proteasome-dependent degradation: stabilization by the pRB tumor suppressor protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 6 ·1997-03-18 ·Pages 2221-6

Campanero MR, Flemington EK

Abstract

The E2F family of transcription factors plays a key role in regulating cell-cycle progression. Accordingly, E2F is itself tightly controlled by a series of transcriptional and posttranscriptional events. Here we provide evidence that E2FI protein levels are regulated by the ubiquitin-proteasome-dependent degradation pathway. An analysis of E2F1 mutants identified a conserved carboxyl-terminal region, which is required for eliciting ubiquitination and protein turnover. Fusion of this E2F1 carboxyl-terminal sequence to a heterologous protein, GAL4, resulted in destabilization of GAL4. Previous studies identified an overlapping region of E2F1 that facilitates complex formation with retinoblastoma tumor suppressor protein, pRB, and we found that pRB blocks ubiquitination and stabilizes E2F1. These results suggest a new mechanism for controlling the cell-cycle regulatory activity of E2F1.

MeSH Terms
Animals Carrier Proteins Cell Cycle Cell Cycle Proteins/metabolism Cell Line Chromatography, Affinity Cysteine Endopeptidases/metabolism DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor Humans Kinetics Multienzyme Complexes/metabolism Osteosarcoma Proteasome Endopeptidase Complex Recombinant Fusion Proteins/biosynthesis,isolation & purification,metabolism Retinoblastoma Protein/metabolism Retinoblastoma-Binding Protein 1 Sequence Deletion Transcription Factor DP1 Transcription Factors/biosynthesis,isolation & purification,metabolism Transcriptional Activation Transfection Tumor Cells, Cultured Ubiquitins/metabolism
Chemicals
Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor E2F1 protein, human Multienzyme Complexes Recombinant Fusion Proteins Retinoblastoma Protein Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors Ubiquitins Cysteine Endopeptidases Proteasome Endopeptidase Complex
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Campanero M R
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Flemington E K
References (34)
34 references, click to expand
  1. Cyclin is degraded by the ubiquitin pathway.
    Nature. 1991 Jan 10;349(6305):132-8 PMID: 1846030
  2. Degradation of E2F by the ubiquitin-proteasome pathway: regulation by retinoblastoma family proteins and adenovirus transforming proteins.
    Genes Dev. 1996 Dec 1;10(23):2960-70 PMID: 8956997
  3. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.
    Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547-51 PMID: 1319065
  4. Retinoblastoma protein switches the E2F site from positive to negative element.
    Nature. 1992 Jul 16;358(6383):259-61 PMID: 1321348
  5. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F.
    Cell. 1992 Jul 24;70(2):337-50 PMID: 1638634
  6. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties.
    Cell. 1992 Jul 24;70(2):351-64 PMID: 1638635
  7. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.
    Science. 1992 Oct 16;258(5081):424-9 PMID: 1411535
  8. Cellular proteolysis. An overview.
    Ann N Y Acad Sci. 1992 Dec 31;674:1-15 PMID: 1288356
  9. E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6914-8 PMID: 8346196
  10. Binding to DNA and the retinoblastoma gene product promoted by complex formation of different E2F family members.
    Science. 1993 Dec 3;262(5139):1557-60 PMID: 8248803
  11. p53 and E2F-1 cooperate to mediate apoptosis.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602-6 PMID: 8170954
  12. Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase.
    Cell. 1994 Jul 15;78(1):161-72 PMID: 8033208
  13. Heterodimerization of the transcription factors E2F-1 and DP-1 is required for binding to the adenovirus E4 (ORF6/7) protein.
    J Virol. 1994 Aug;68(8):5027-35 PMID: 8035503
  14. Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain.
    Cell. 1994 Sep 9;78(5):787-98 PMID: 8087846
  15. Differential regulation of E2F transactivation by cyclin/cdk2 complexes.
    Genes Dev. 1994 Aug 1;8(15):1772-86 PMID: 7958856
  16. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis.
    Mol Cell Biol. 1994 Dec;14(12):8166-73 PMID: 7969153
  17. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10918-22 PMID: 7971984
  18. Oncogenic capacity of the E2F1 gene.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12823-7 PMID: 7809128
  19. Multiple members of the E2F transcription factor family are the products of oncogenes.
    Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1357-61 PMID: 7877982
  20. E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis.
    J Virol. 1995 Apr;69(4):2491-500 PMID: 7884898
  21. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin.
    Science. 1995 May 5;268(5211):726-31 PMID: 7732382
  22. The retinoblastoma protein and cell cycle control.
    Cell. 1995 May 5;81(3):323-30 PMID: 7736585
  23. In vivo association of E2F and DP family proteins.
    Mol Cell Biol. 1995 May;15(5):2536-46 PMID: 7739537
  24. Mechanism of active transcriptional repression by the retinoblastoma protein.
    Nature. 1995 Jun 29;375(6534):812-5 PMID: 7596417
  25. Ubiquitin, proteasomes, and the regulation of intracellular protein degradation.
    Curr Opin Cell Biol. 1995 Apr;7(2):215-23 PMID: 7612274
  26. A new twist to the cell cycle.
    Science. 1995 Aug 4;269(5224):631-2 PMID: 7624789
  27. Selective protein degradation: a journey's end within the proteasome.
    Cell. 1995 Sep 22;82(6):881-4 PMID: 7553848
  28. A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.
    Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11544-8 PMID: 8524800
  29. Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint.
    Cell. 1995 Dec 29;83(7):1149-58 PMID: 8548802
  30. Tumor induction and tissue atrophy in mice lacking E2F-1.
    Cell. 1996 May 17;85(4):537-48 PMID: 8653789
  31. E2F-1 functions in mice to promote apoptosis and suppress proliferation.
    Cell. 1996 May 17;85(4):549-61 PMID: 8653790
  32. mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect.
    J Biol Chem. 1996 Oct 18;271(42):25906-11 PMID: 8824223
  33. The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway.
    Genes Dev. 1996 Dec 1;10(23):2949-59 PMID: 8956996
  34. Identification of a growth suppression domain within the retinoblastoma gene product.
    Genes Dev. 1992 Jun;6(6):953-64 PMID: 1534305
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.6.2221
Published
1997-03-18
Pages
2221-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20068
Subset
IM
Grants
NIGMS NIH HHS · R01 GM048045 · United States
NCI NIH HHS · CA47554 · United States
NIGMS NIH HHS · R29 GM48045 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.6.2221 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