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In situ Subcellular Fractionation of Adherent and Non-adherent Mammalian Cells
Published on: July 24, 2010
The viral oncoproteins Ad5 E1A, HPV16 E7 and SV40 TAg bind a common region of the TBP-associated factor-110
J M Mazzarelli1, G B Atkins, J V Geisberg
1Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
A function shared by the adenovirus E1A, papillomavirus E7 and SV40 TAg oncoproteins is their ability to interfere with normal cell growth by interacting with members of the retinoblastoma protein family. In this study, we show that each of these oncoproteins can also bind to the 921 amino acid TBP-associated factor-110 (TAF-110). The significance of the binding is underscored by the observation that each oncoprotein binds to the same 77 amino acid carboxyl region of TAF-110. In the case of E1A and TAg, this finding is consistent with their abilities to stimulate transcription initiation, in part, through their known interactions with TBP. While it is not clear whether E7 can also activate promoters through protein:protein interactions with components of the transcription initiation complex, our demonstration that E7 can bind to TAF-110, as well as TBP, suggests that E7 may modulate the expression of specific promoters which could contribute to the pathogenesis of human papillomavirus.
Insights
Oncoproteins from adenovirus E1A, papillomavirus E7, and SV40 TAg bind to TBP-associated factor-110 (TAF-110). This interaction, occurring in the same TAF-110 region, suggests a role in cell growth regulation and viral pathogenesis.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- Oncoproteins like adenovirus E1A, papillomavirus E7, and SV40 TAg disrupt normal cell growth.
- These oncoproteins are known to interact with retinoblastoma protein family members.
Purpose of the Study:
- To investigate the interaction between E1A, E7, and TAg oncoproteins and TBP-associated factor-110 (TAF-110).
- To determine the specific binding region of TAF-110 for these oncoproteins.
- To explore the functional implications of these interactions in viral pathogenesis.
Main Methods:
- Protein binding assays were used to demonstrate interactions.
- The carboxyl region of TAF-110 was identified as the binding site for the oncoproteins.
Main Results:
- Adenovirus E1A, papillomavirus E7, and SV40 TAg oncoproteins all bind to TAF-110.
- The binding occurs within the same 77 amino acid carboxyl region of TAF-110.
- E1A and TAg binding to TAF-110 is consistent with their known roles in transcription initiation via TBP interactions.
Conclusions:
- Oncoproteins E1A, E7, and TAg interact with TAF-110, suggesting a common mechanism for cell growth interference.
- Papillomavirus E7's interaction with TAF-110, in addition to TBP, may contribute to human papillomavirus pathogenesis by modulating specific promoter expression.
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