Self-association of adenovirus type 5 E1B-55 kDa as well as p53 is essential for their mutual interaction.
The adenovirus type 5 E1B-55 kDa oncoprotein forms a complex with the tumor suppressor p53 and inactivates it. E1B-55 kDa and p53 are each capable of forming oligomers. We mapped the oligomerization domain of E1B-55 kDa to the central portion of the protein. Disturbing E1B-55 kDa self-association by point mutations at residues 285/286 or 307 not only impairs its intracellular localization to the cytoplasmic clusters, but in addition, its association with p53. Strikingly, tetramerization of p53 is also required for efficient association with E1B-55 kDa. Moreover, two different E1B-55 kDa mutants defective for p53 binding but proficient for oligomerization can trans-complement each other for p53 relocalization. We propose that the homo-oligomerization of each component enables efficient interaction between E1B-55 kDa and p53 through increased avidity.
Morawska-Onyszczuk
M
M
Department of Molecular Oncology, Göttingen Center of Molecular Bioscience, Ernst Caspari Haus, University of Göttingen, Göttingen 37077, Germany.
Bieńkowska-Szewczyk
K
K
Dobbelstein
M
M
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000257:Adenoviridae Infections / Q000235:genetics / Q000378:metabolism; D017501:Adenovirus E1B Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis; D002453:Cell Cycle; D018388:Codon, Terminator / Q000235:genetics; D006801:Humans; D008970:Molecular Weight; D017354:Point Mutation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D017501:Adenovirus E1B Proteins; D018388:Codon, Terminator; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2