title: Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes.
abstract: Sequence-specific single-stranded DNA-binding protein 2 (SSBP2) is a candidate tumor suppressor for human acute myelogenous leukemia (AML). Inducible expression of SSBP2 causes growth arrest and partial differentiation in AML cells. Here, we report that the adenoviral oncoprotein E1B55K directly binds to endogenous SSBP2 protein and sequesters it into juxtanuclear bodies in adenovirally transformed human embryonic kidney (HEK) 293 cells. Similarly, transient expression of E1B55K in IMR90 fibroblasts and HeLa cells result in the formation of juxtanuclear bodies containing SSBP2. When nuclear export of E1B55K is prevented, SSBP2 remains associated with E1B55K in nuclear foci. A requirement for intact microtubules to retain the integrity of the juxtanuclear bodies suggests them to be E1B55K containing aggresomes. The adenoviral E1B55K protein has been shown to localize to the Mre11 complex and p53 to aggresome structures; together with the viral E4orf6 protein, E1B55K recruits a cellular E3 ubiquitin ligase that induces degradation of Mre11 and p53. However, our present studies reveal that E1B55K does not degrade SSBP2. These data demonstrate that E1B55K targets the candidate leukemia suppressor SSBP2 and suggest that subverting its function may contribute to cell transformation by viral oncoproteins.
authors.affiliation: Department of Molecular Genetics, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Fleisig
authors.forename: N I
authors.initials: NI
authors.lastname: Orazio
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.forename: A F
authors.initials: AF
authors.lastname: Tyler
authors.forename: H P
authors.initials: HP
authors.lastname: Adams
authors.forename: M D
authors.initials: MD
authors.lastname: Weitzman
authors.forename: L
authors.initials: L
authors.lastname: Nagarajan
mesh_terms: D017766:Acid Anhydride Hydrolases; D000208:Acute Disease; D017501:Adenovirus E1B Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D002479:Inclusion Bodies / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology; D000076228:MRE11 Homologue Protein; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D017501:Adenovirus E1B Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D011993:Recombinant Fusion Proteins; C477058:SSBP2 protein, human; D049452:Green Fluorescent Proteins; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes