title: Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies.
abstract: The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells due to the expression of the PML-RAR alpha hybrid. Here we report that adenovirus infection causes a drastic redistribution of PML from spherical nuclear bodies into fibrous structures. The product encoded by adenovirus E4-ORF3 is shown to be responsible for this reorganization and to colocalize with PML into these fibers. In addition, we demonstrate that E1A oncoproteins concentrate in the PML domains, both in infected and transiently transfected cells, and that this association requires the conserved amino acid motif (D)LXCXE, common to all viral oncoproteins that bind pRB or the related p107 and p130 proteins. The SV-40 large T antigen, another member of this oncoprotein family is also found in close association with the PML nuclear bodies. Taken together, the present data indicate that the subnuclear domains containing PML represent a preferential target for DNA tumor viruses, and therefore suggest a more general involvement of the PML nuclear bodies in oncogenic processes.
authors.affiliation: Instituto de Histologia, Faculdade de Medicina, Lisboa, Portugal.
authors.forename: T
authors.initials: T
authors.lastname: Carvalho
authors.forename: J S
authors.initials: JS
authors.lastname: Seeler
authors.forename: K
authors.initials: K
authors.lastname: Ohman
authors.forename: P
authors.initials: P
authors.lastname: Jordan
authors.forename: U
authors.initials: U
authors.lastname: Pettersson
authors.forename: G
authors.initials: G
authors.lastname: Akusjärvi
authors.forename: M
authors.initials: M
authors.lastname: Carmo-Fonseca
authors.forename: A
authors.initials: A
authors.lastname: Dejean
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D017504:Adenovirus E4 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001422:Bacterial Adhesion; D001426:Bacterial Proteins; D006367:HeLa Cells / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D015530:Nuclear Matrix / Q000378:metabolism*; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000378:metabolism; D016366:Open Reading Frames; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D017500:Adenovirus E1A Proteins; D017504:Adenovirus E4 Proteins; D000952:Antigens, Polyomavirus Transforming; D001426:Bacterial Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human