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PMID: 2173783 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Chemical synthesis of human papillomavirus type 16 E7 oncoprotein: autonomous protein domains for induction of cellular DNA synthesis and for trans activation.

Journal of virology ·Vol. 64 ·No. 12 ·1990-12-00 ·Pages 6121-9

Rawls JA, Pusztai R, Green M

Abstract

The human papillomavirus type 16 E7 protein belongs to a family of nuclear oncoproteins that share amino acid sequences and functional homology. To localize biochemical activities associated with E7, we chemically synthesized the full-length 98-amino-acid polypeptide and several deletion mutant peptides. We show that the E7 polypeptide is biologically active and possesses at least two functional domains; the first induces cellular DNA synthesis in quiescent rodent cells, and the second trans activates the adenovirus E1A-inducible early E2 promoter and binds zinc. Further, each domain is autonomous and can function on separate peptides. DNA synthesis induction activity maps within the N-terminal portion of the molecule, which contains sequences related to adenovirus E1A conserved domains 1 and 2 required for cell transformation and binding of the retinoblastoma gene product. trans-Activation and Zn-binding activities map within the C-terminal portion of the molecule, a region which contains Cys-X-X-Cys motifs. trans Activation does not require protein synthesis, implying a mechanism that involves interaction with a preexisting cellular factor(s). E7 trans activates the adenovirus E2 promoter but not other E1A-inducible viral promoters, suggesting the possibility that E7 trans activation involves interaction, directly or indirectly, with cellular transcription factor E2F.

MeSH Terms
Adenoviruses, Human/genetics Amino Acid Sequence Cell Transformation, Viral Genes, Viral HeLa Cells/metabolism Humans Kinetics Molecular Sequence Data Molecular Weight Oncogene Proteins, Viral/chemical synthesis,metabolism Papillomaviridae/genetics,metabolism Papillomavirus E7 Proteins Peptides/chemical synthesis Promoter Regions, Genetic Protein Binding Protein-Tyrosine Kinases/chemical synthesis Transcriptional Activation Zinc/metabolism
Chemicals
Oncogene Proteins, Viral Papillomavirus E7 Proteins Peptides oncogene protein E7, Human papillomavirus type 16 Protein-Tyrosine Kinases Zinc
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Rawls J A
Institute for Molecular Virology, St. Louis University Medical Center, Missouri 63110.
Pusztai R
Green M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.64.12.6121-6129.1990
Published
1990-12-00
Pages
6121-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC248786
Subset
IM
Grants
NIAID NIH HHS · 5 K06 AI04739 · United States
NCI NIH HHS · CA28689 · United States
NCI NIH HHS · CA29561 · United States
External Links
PubMed source DOI: 10.1128/JVI.64.12.6121-6129.1990 PMC Full Text View journal details
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