title: The adenovirus 55 residue E1A protein is a transcriptional activator and binds the unliganded thyroid hormone receptor.
abstract: The early region 1A (E1A) of human adenovirus types 2 and 5 is differentially spliced to yield five distinct mRNAs that encode different proteins. The smallest E1A RNA transcript encodes a 55 residue (55R) protein that shares only 28 amino acid residues with the other E1A proteins. Even though it is the most abundant E1A transcript at late times post-infection, little is known about the functions of this E1A isoform. In this study, we show that the E1A 55R protein interacts with, and modulates the activity of the unliganded thyroid hormone receptor (TR). We demonstrate that E1A 55R contains a signature motif known as the CoRNR box that confers interaction with the unliganded TR; this motif was originally identified in cellular corepressors. Using a system reconstituted in the yeast Saccharomyces cerevisiae, which lack endogenous TR and TR coregulators, we show that E1A 55R nonetheless differs from cellular corepressors as it functions as a strong co-activator of TR-dependent transcription and that it possesses an intrinsic transcriptional activation domain. These data indicate that the E1A 55R protein functions as a transcriptional regulator.
authors.affiliation: Departments of Oncology, Microbiology & Immunology, University of Western Ontario and London Regional Cancer Centre, London, Ontario N6A 4L6, Canada.
authors.forename: Vishnuka D
authors.initials: VD
authors.lastname: Arulsundaram
authors.affiliation: The Methodist Hospital Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Webb
authors.affiliation: Masdar Institute of Science and Technology, Abu Dhabi, UAE.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Yousef
authors.affiliation: Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Pelka
authors.affiliation: Departments of Oncology, Microbiology & Immunology, University of Western Ontario and London Regional Cancer Centre, London, Ontario N6A 4L6, Canada.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Fonseca
authors.affiliation: The Methodist Hospital Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Baxter
authors.affiliation: Department of Medicine, Endocrine Division, Mount Sinai Hospital, University of Toronto Medical School, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Walfish
authors.affiliation: Departments of Oncology, Microbiology & Immunology, University of Western Ontario and London Regional Cancer Centre, London, Ontario N6A 4L6, Canada.
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mymryk
mesh_terms: D017500:Adenovirus E1A Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000258:Adenovirus Infections, Human / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D000260:Adenoviruses, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D017500:Adenovirus E1A Proteins; D011988:Receptors, Thyroid Hormone; D015534:Trans-Activators