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PMID: 10082529 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Synergism with germ line transcription factor Oct-4: viral oncoproteins share the ability to mimic a stem cell-specific activity.

Molecular and cellular biology ·Vol. 19 ·No. 4 ·1999-04-00 ·Pages 2635-43

Brehm A, Ohbo K, Zwerschke W, Botquin V, Jansen-Dürr P, Schöler HR

Abstract

Activation of transcription by Oct-4 from remote binding sites requires a cofactor that is restricted to embryonal stem cells. The adenovirus E1A protein can mimic the activity of this stem cell-specific factor and stimulates Oct-4 activity in differentiated cells. Here we characterize the Oct-4-E1A interaction and show that the E1A 289R protein harbors two independent Oct-4 binding sites, both of which specifically interact with the POU domain of Oct-4. Furthermore, we demonstrate that, like E1A, the human papillomavirus E7 oncoprotein also specifically binds to the Oct-4 POU domain. E7 and Oct-4 can form a complex both in vitro and in vivo. Expression of E7 in differentiated cells stimulates Oct-4-mediated transactivation from distal binding sites. Moreover, Oct-4, but not other Oct factors, is active when expressed in cells transformed by human papillomavirus. Our results suggest that different viruses have evolved oncoproteins that share the ability to target Oct-4 and to mimic a stem cell-specific activity.

MeSH Terms
Adenovirus E1A Proteins/metabolism Binding Sites Cell Differentiation Cell Transformation, Viral DNA-Binding Proteins/metabolism Molecular Mimicry Octamer Transcription Factor-3 Oncogene Proteins, Viral/metabolism POU Domain Factors Papillomaviridae Papillomavirus E7 Proteins Protein Binding Stem Cells/physiology Transcription Factors Transcriptional Activation
Chemicals
Adenovirus E1A Proteins DNA-Binding Proteins Octamer Transcription Factor-3 Oncogene Proteins, Viral POU Domain Factors Papillomavirus E7 Proteins Transcription Factors oncogene protein E7, Human papillomavirus type 16
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Brehm A
Gene Expression Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Federal Republic of Germany.
Ohbo K
Zwerschke W
Botquin V
Jansen-Dürr P
Schöler H R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.4.2635
Published
1999-04-00
Pages
2635-43
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84056
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.4.2635 PMC Full Text View journal details
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