title: Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation.
abstract: We have investigated the requirements for CRM1-mediated nuclear export and SUMO1 conjugation of the adenovirus E1B-55K protein during productive infection. Our data show that CRM1 is the major export receptor for E1B-55K in infected cells. Functional inactivation of the E1B-55K CRM1-dependent nuclear export signal (NES) or leptomycin B treatment causes an almost complete redistribution of the viral protein from the cytoplasm to the nucleus and its accumulation at the periphery of the viral replication centers. Interestingly, however, this nuclear restriction imposed on the wild type and the NES mutant protein is fully compensated by concurrent inactivation of the adjacent SUMO1 conjugation site. Moreover, the same mutation fully reverses defects of the NES mutant in the nucleocytoplasmic transport of Mre11 and proteasomal degradation of p53. These results show that nuclear export of E1B-55K in infected cells occurs via CRM1-dependent and -independent pathways and suggest that SUMO1 conjugation and deconjugation provide a molecular switch that commits E1B-55K to a CRM1-independent export pathway.
authors.affiliation: Heinrich Pette Institute for Experimental Virology and Immunology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kindsmüller
authors.forename: Peter
authors.initials: P
authors.lastname: Groitl
authors.forename: Barbara
authors.initials: B
authors.lastname: Härtl
authors.forename: Paola
authors.initials: P
authors.lastname: Blanchette
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.forename: Thomas
authors.initials: T
authors.lastname: Dobner
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D008969:Molecular Sequence Data; D049790:Nuclear Export Signals / Q000502:physiology; D011817:Rabbits; D051381:Rats; D025842:SUMO-1 Protein / Q000378:metabolism / Q000502:physiology*
chemical_list: D017501:Adenovirus E1B Proteins; D049790:Nuclear Export Signals; D025842:SUMO-1 Protein