Adenovirus early region 1A (E1A) is a gene expressed during adenovirus replication to produce a variety of E1A proteins.[1] It is expressed during the early phase of the viral life span.
E1A encodes two major proteins in Ad5, translated after alternative splicing of the viral DNA transcript, that are able to cause a variety of different effects in mammalian cells.[2] The proteins encoded by E1A tend to localize in the nucleus and affect genetic regulation by the host cell.[1] After viral infection, they stimulate expression of other viral genes and can either enhance or repress expression of cellular genes depending on cellular context and coordination with other viral genes.[3]
The addition of E1A DNA into cells may cause adverse biological effects,[4] such as increasing p53 expression,[5] stimulating DNA synthesis and cell cycle progression in quiescent cells,[2] and inhibiting differentiation.[6] It has been considered an oncogene.[7] It can also behave as a tumour suppressor gene.[8][3]
- ^ a b "Introduction To Ad5 E1A".
- ^ a b Molloy DP, Smith KJ, Milner AE, Gallimore PH, Grand RJ (February 1999). "The structure of the site on adenovirus early region 1A responsible for binding to TATA-binding protein determined by NMR spectroscopy". The Journal of Biological Chemistry. 274 (6): 3503–3512. doi:10.1074/jbc.274.6.3503. PMID 9920896.
- ^ a b Frisch SM, Mymryk JS (June 2002). "Adenovirus-5 E1A: paradox and paradigm". Nature Reviews. Molecular Cell Biology. 3 (6): 441–452. doi:10.1038/nrm827. PMID 12042766. S2CID 20282450.
- ^ Boulanger PA, Blair GE (April 1991). "Expression and interactions of human adenovirus oncoproteins". The Biochemical Journal. 275 ( Pt 2) (Pt 2): 281–299. doi:10.1042/bj2750281. PMC 1150051. PMID 1827253.
- ^ Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E (August 1992). "The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins". Proceedings of the National Academy of Sciences of the United States of America. 89 (16): 7742–7746. Bibcode:1992PNAS...89.7742R. doi:10.1073/pnas.89.16.7742. PMC 49787. PMID 1457005.
- ^ Webster KA, Muscat GE, Kedes L (April 1988). "Adenovirus E1A products suppress myogenic differentiation and inhibit transcription from muscle-specific promoters". Nature. 332 (6164): 553–557. Bibcode:1988Natur.332..553W. doi:10.1038/332553a0. PMID 2965790. S2CID 4355283.
- ^ Routes JM, Ryan S, Clase A, Miura T, Kuhl A, Potter TA, Cook JL (October 2000). "Adenovirus E1A oncogene expression in tumor cells enhances killing by TNF-related apoptosis-inducing ligand (TRAIL)". Journal of Immunology. 165 (8): 4522–4527. doi:10.4049/jimmunol.165.8.4522. PMID 11035092.
- ^ Frisch SM (May 2004). "E1A as a tumor suppressor gene: commentary re S. Madhusudan et al. A multicenter Phase I gene therapy clinical trial involving intraperitoneal administration of E1A-lipid complex in patients with recurrent epithelial ovarian cancer overexpressing HER-2/neu oncogene". Clinical Cancer Research. 10 (9): 2905–2907. doi:10.1158/1078-0432.CCR-04-0644. PMID 15131023.