title: Recruitment of the priming protein pTP and DNA binding occur by overlapping Oct-1 POU homeodomain surfaces.
abstract: The human transcription factor Oct-1 can stimulate transcription from a variety of promoters by interacting with the coactivators OBF-1/OCA-B/BOB-1, SNAP190 and VP16. These proteins contact Oct-1 regions different from the DNA binding surface. Oct-1 also stimulates the DNA replication of adenovirus through its DNA binding site in the origin. The Oct-1 POU homeodomain (POUhd) binds the adenovirus precursor terminal protein pTP, which serves as the protein primer of DNA replication and recruits pTP to the origin. To map the interaction with pTP at the POUhd surface, we screened a library of randomly mutated POU domains and identified mutations that interfered with pTP interaction and DNA replication stimulation. These mutants clustered at a surface different from those recognized by OBF-1, SNAP190 and VP16. Unexpectedly, the pTP binding region largely overlapped with the DNA binding surface of POUhd. In agreement with this, pTP binding and DNA binding were mutually exclusive. We propose a model to reconcile pTP recruitment and DNA binding by Oct-1.
authors.affiliation: Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: R N
authors.initials: RN
authors.lastname: de Jong
authors.forename: M E
authors.initials: ME
authors.lastname: Mysiak
authors.forename: L A T
authors.initials: LA
authors.lastname: Meijer
authors.forename: M
authors.initials: M
authors.lastname: van der Linden
authors.forename: P C
authors.initials: PC
authors.lastname: van der Vliet
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D010750:Phosphoproteins / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014764:Viral Proteins
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D010750:Phosphoproteins; D011498:Protein Precursors; D014157:Transcription Factors; D014764:Viral Proteins; C085476:pTP protein, adenovirus