Home LiteratureArticle Details
PMID: 16061792 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 32 ·2005-08-09 ·Pages 11492-7

Huh KW, DeMasi J, Ogawa H, Nakatani Y, Howley PM, Münger K

Abstract

The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130. However, there is ample evidence that E7 has additional cellular targets that contribute to its transforming potential. We isolated HPV-16 E7 associated cellular protein complexes by tandem affinity purification and mass spectrometry and identified the 600-kDa retinoblastoma protein associated factor, p600, as a cellular target of E7. Association of E7 with p600 is independent of the pocket proteins and is mediated through the N terminal E7 domain, which is related to conserved region 1 of the adenovirus E1A protein and importantly contributes to cellular transformation independent of pRB binding. Depletion of p600 protein levels by RNA interference substantially decreased anchorage-independent growth in HPV-positive and -negative human cancer cells. Therefore, p600 is a cellular target of E7 that regulates cellular pathways that contribute to anchorage-independent growth and cellular transformation.

MeSH Terms
Calmodulin-Binding Proteins/metabolism Cell Proliferation Cell Transformation, Viral/genetics HeLa Cells Humans Immunoprecipitation Mass Spectrometry Microscopy, Fluorescence Multiprotein Complexes/isolation & purification,metabolism Oncogene Proteins, Viral/metabolism Papillomaviridae/metabolism Papillomavirus E7 Proteins Protein Binding RNA Interference
Chemicals
Calmodulin-Binding Proteins Multiprotein Complexes Oncogene Proteins, Viral Papillomavirus E7 Proteins oncogene protein E7, Human papillomavirus type 16
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Huh Kyung-Won
The Channing Laboratory, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
DeMasi Joseph
Ogawa Hidesato
Nakatani Yoshihiro
Howley Peter M
Münger Karl
References (42)
42 references, click to expand
  1. The N-end rule and regulation of apoptosis.
    Nat Cell Biol. 2003 May;5(5):373-6 PMID: 12724766
  2. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5523-7 PMID: 1648218
  3. Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members.
    J Virol. 2003 Nov;77(22):12331-5 PMID: 14581569
  4. Recapitulation of the effects of the human papillomavirus type 16 E7 oncogene on mouse epithelium by somatic Rb deletion and detection of pRb-independent effects of E7 in vivo.
    Mol Cell Biol. 2003 Dec;23(24):9094-103 PMID: 14645521
  5. Immunoaffinity purification of mammalian protein complexes.
    Methods Enzymol. 2003;370:430-44 PMID: 14712665
  6. Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins.
    Int J Cancer. 2004 Mar 20;109(2):157-62 PMID: 14750163
  7. Role of the retinoblastoma pathway in senescence triggered by repression of the human papillomavirus E7 protein in cervical carcinoma cells.
    Cancer Res. 2004 May 1;64(9):3079-86 PMID: 15126344
  8. Mechanisms of human papillomavirus-induced oncogenesis.
    J Virol. 2004 Nov;78(21):11451-60 PMID: 15479788
  9. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells.
    Nature. 1985 Mar 7-13;314(6006):111-4 PMID: 2983228
  10. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines.
    Am J Pathol. 1985 Jun;119(3):361-6 PMID: 2990217
  11. Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines.
    J Virol. 1987 Apr;61(4):962-71 PMID: 3029430
  12. Expression of RB and p53 proteins in HPV-positive and HPV-negative cervical carcinoma cell lines.
    Mol Carcinog. 1991;4(3):171-5 PMID: 1648361
  13. Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein.
    J Virol. 1992 Apr;66(4):2418-27 PMID: 1312637
  14. N-recognin/Ubc2 interactions in the N-end rule pathway.
    J Biol Chem. 1993 Jun 5;268(16):12046-54 PMID: 8505328
  15. Negative regulation of the bovine papillomavirus E5, E6, and E7 oncogenes by the viral E1 and E2 genes.
    J Virol. 1995 Jan;69(1):395-402 PMID: 7983735
  16. Mutations in the Drosophila pushover gene confer increased neuronal excitability and spontaneous synaptic vesicle fusion.
    Genetics. 1996 Apr;142(4):1215-23 PMID: 8846899
  17. E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway.
    Cancer Res. 1996 Oct 15;56(20):4620-4 PMID: 8840974
  18. Analysis of the p53-mediated G1 growth arrest pathway in cells expressing the human papillomavirus type 16 E7 oncoprotein.
    J Virol. 1997 Apr;71(4):2905-12 PMID: 9060648
  19. Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis.
    Virology. 1997 Dec 8;239(1):97-107 PMID: 9426450
  20. The human papillomavirus-16 E6 oncoprotein decreases the vigilance of mitotic checkpoints.
    Oncogene. 1997 Dec 18;15(25):3025-35 PMID: 9444951
  21. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  22. Papillomavirus E2 induces senescence in HPV-positive cells via pRB- and p21(CIP)-dependent pathways.
    EMBO J. 2000 Nov 1;19(21):5762-71 PMID: 11060027
  23. Degradation of the E7 human papillomavirus oncoprotein by the ubiquitin-proteasome system: targeting via ubiquitination of the N-terminal residue.
    Oncogene. 2000 Nov 30;19(51):5944-50 PMID: 11127826
  24. Destabilization of the retinoblastoma tumor suppressor by human papillomavirus type 16 E7 is not sufficient to overcome cell cycle arrest in human keratinocytes.
    J Virol. 2001 Aug;75(15):6737-47 PMID: 11435552
  25. Degradation of the retinoblastoma tumor suppressor by the human papillomavirus type 16 E7 oncoprotein is important for functional inactivation and is separable from proteasomal degradation of E7.
    J Virol. 2001 Aug;75(16):7583-91 PMID: 11462030
  26. BIG: a calossin-like protein required for polar auxin transport in Arabidopsis.
    Genes Dev. 2001 Aug 1;15(15):1985-97 PMID: 11485992
  27. Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways.
    Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10445-50 PMID: 11517334
  28. Biological activities and molecular targets of the human papillomavirus E7 oncoprotein.
    Oncogene. 2001 Nov 26;20(54):7888-98 PMID: 11753671
  29. Papillomaviruses and cancer: from basic studies to clinical application.
    Nat Rev Cancer. 2002 May;2(5):342-50 PMID: 12044010
  30. Stable suppression of tumorigenicity by virus-mediated RNA interference.
    Cancer Cell. 2002 Sep;2(3):243-7 PMID: 12242156
  31. RING finger ubiquitin protein ligases: implications for tumorigenesis, metastasis and for molecular targets in cancer.
    Semin Cancer Biol. 2003 Feb;13(1):5-14 PMID: 12507552
  32. CDD: a curated Entrez database of conserved domain alignments.
    Nucleic Acids Res. 2003 Jan 1;31(1):383-7 PMID: 12520028
  33. The mouse and human genes encoding the recognition component of the N-end rule pathway.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7898-903 PMID: 9653112
  34. Intrinsic tumour suppression.
    Nature. 2004 Nov 18;432(7015):307-15 PMID: 15549092
  35. Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding.
    Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11486-91 PMID: 16081543
  36. The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A.
    Cell. 1988 May 20;53(4):539-47 PMID: 2836062
  37. Functional similarity between HPV16E7, SV40 large T and adenovirus E1a proteins.
    Oncogene. 1989 Feb;4(2):153-8 PMID: 2538790
  38. A point mutational analysis of human papillomavirus type 16 E7 protein.
    J Virol. 1989 Jun;63(6):2650-6 PMID: 2542578
  39. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product.
    EMBO J. 1989 Dec 20;8(13):4099-105 PMID: 2556261
  40. The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties.
    J Virol. 1990 Feb;64(2):723-30 PMID: 2153238
  41. Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells.
    Oncogene. 1990 Sep;5(9):1383-9 PMID: 2216461
  42. Mutations in the huge Arabidopsis gene BIG affect a range of hormone and light responses.
    Plant J. 2003 Jul;35(1):57-70 PMID: 12834402
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.0505337102
Published
2005-08-09
Epub
2005-00-01
Pages
11492-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1182135
Subset
IM
Grants
NCI NIH HHS · P01 CA050661 · United States
NCI NIH HHS · R01 CA081135 · United States
NCI NIH HHS · P01-CA050661 · United States
NCI NIH HHS · R01-CA081135 · United States
External Links
PubMed source DOI: 10.1073/pnas.0505337102 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