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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Interaction between human cyclin A and adenovirus E1A-associated p107 protein
Abstract:
The products of the adenovirus early region 1A (E1A) gene are potent oncoproteins when tested in standard transformation and immortalization assays. Many of the changes induced by E1A may be due to its interaction with cellular proteins. Four of these cellular proteins are the retinoblastoma protein (pRB), p107, cyclin A, and p33cdk2. The pRB and p107 proteins are structurally related and have several characteristics in common, including that they both bind to the SV40 large T oncoprotein as well as to E1A. Cyclin A and p33cdk2 are thought to function in the control of the cell cycle. They bind to one another, forming a kinase that closely resembles the cell cycle-regulating complexes containing p34cdc2. Cyclin A is now shown to bind to p107 in the absence of E1A. The association of p107 with cyclin A suggests a direct link between cell cycle control and the function of p107.
Insights
Adenovirus E1A oncoproteins interact with cellular proteins like pRB and p107. New findings show cyclin A binds p107, linking cell cycle control to p107 function.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- Adenovirus early region 1A (E1A) gene products are potent oncoproteins.
- E1A-induced cellular changes are mediated through interactions with cellular proteins.
- Key E1A-interacting proteins include retinoblastoma protein (pRB), p107, cyclin A, and p33cdk2.
Purpose of the Study:
- To investigate the interactions between E1A-associated cellular proteins.
- To determine the relationship between p107 and cell cycle regulators like cyclin A.
- To elucidate the functional implications of these protein interactions.
Main Methods:
- Co-immunoprecipitation assays to study protein binding.
- Analysis of protein interactions in the presence and absence of E1A.
- Biochemical characterization of protein complexes.
Main Results:
- pRB and p107 are structurally related and bind to both E1A and SV40 large T oncoprotein.
- Cyclin A and p33cdk2 form a kinase complex involved in cell cycle control.
- Cyclin A directly binds to p107 independently of E1A.
Conclusions:
- The direct association of p107 with cyclin A establishes a link between p107 function and cell cycle regulation.
- These findings provide new insights into the mechanisms by which viral oncoproteins subvert cellular processes.
- Understanding these interactions is crucial for deciphering viral oncogenesis and cellular transformation.
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