Adenovirus and cell cycle control.
Adenovirus infection of quiescent cells induces transition from G0 or G1 into the S phase of the cell cycle and allows cellular proliferation. This is beneficial for the virus since cells in S phase provide optimal conditions for viral replication. Adenovirus E1A, E1B and E4 gene products contribute to cell cycle deregulation. E1A proteins inactivate the pRb checkpoint, allowing the E2F transcription factor to activate genes involved in nucleotide metabolism and DNA replication, which are required in S phase. E1A also interacts with transcriptional modulators, including histone acetyltransferases, histone deacetylases, and other chromatin remodeling factors. These interactions affect transcription of several cellular and viral genes, some of which are involved in cell cycle regulation. Cell cycle deregulation by E1A results in stabilization and accumulation of p53. To prevent cell cycle arrest and apoptosis that would be triggered by p53, the adenovirus E1B and E4orf6 gene products employ various mechanisms to inactivate the tumor suppressor. Additional E4 gene products also interact with and modulate cell cycle regulators. Cell cycle checkpoints targeted by adenovirus proteins are often compromised in human tumors as well. Thus, understanding the interactions between adenovirus and the cell cycle has facilitated the generation of adenovirus mutants, which can replicate only in cells with inactivated checkpoints. Such "oncolytic" viruses are being tested for their ability to specifically replicate in and lyse cancer cells.
Ben-Israel
Haggit
H
The Gonda Center of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Kleinberger
Tamar
T
D000256:Adenoviridae / Q000254:growth & development / Q000502:physiology*; D017500:Adenovirus E1A Proteins / Q000502:physiology; D017501:Adenovirus E1B Proteins / Q000502:physiology; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D018797:Cell Cycle Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53