title: Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation.
abstract: Hub proteins have central roles in regulating cellular processes. By targeting a single cellular hub, a viral oncogene may gain control over an entire module in the cellular interaction network that is potentially comprised of hundreds of proteins. The adenovirus E1A oncoprotein is a viral hub that interacts with many cellular hub proteins by short linear motifs/molecular recognition features (MoRFs). These interactions transform the architecture of the cellular protein interaction network and virtually reprogram the cell. To identify additional MoRFs within E1A, we screened portions of E1A for their ability to activate yeast pseudohyphal growth or differentiation. This identified a novel functional region within E1A conserved region 2 comprised of the sequence EVIDLT. This MoRF is necessary and sufficient to bind the N-terminal region of the SUMO conjugase UBC9, which also interacts with SUMO noncovalently and is involved in polySUMOylation. Our results suggest that E1A interferes with polySUMOylation, but not with monoSUMOylation. These data provide the first insight into the consequences of the interaction of E1A with UBC9, which was initially described in 1996. We further demonstrate that polySUMOylation regulates pseudohyphal growth and promyelocytic leukemia body reorganization by E1A. In conclusion, the interaction of the E1A oncogene with UBC9 mimics the normal binding between SUMO and UBC9 and represents a novel mechanism to modulate polySUMOylation.
authors.affiliation: Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: A F
authors.initials: AF
authors.lastname: Yousef
authors.forename: G J
authors.initials: GJ
authors.lastname: Fonseca
authors.forename: P
authors.initials: P
authors.lastname: Pelka
authors.forename: J N G
authors.initials: JN
authors.lastname: Ablack
authors.forename: C
authors.initials: C
authors.lastname: Walsh
authors.forename: F A
authors.initials: FA
authors.lastname: Dick
authors.forename: D P
authors.initials: DP
authors.lastname: Bazett-Jones
authors.forename: G S
authors.initials: GS
authors.lastname: Shaw
authors.forename: J S
authors.initials: JS
authors.lastname: Mymryk
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025842:SUMO-1 Protein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D017500:Adenovirus E1A Proteins; C110690:FLO11 protein, S cerevisiae; D008562:Membrane Glycoproteins; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9