The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif.
BS69 is a transcriptional co-repressor protein and a potential tumor suppressor that binds to the adenoviral oncoprotein E1A. We show that the C-terminal Mynd domain of BS69 (amino acids 516-561) or the closely related Mynd domains of the Caenorhabditis elegans proteins Bra-1 and Bra-2 bind not only to E1A but also to the Epstein-Barr virus EBNA2 oncoprotein and the Myc-related cellular protein MGA. Interaction depends on intact PXLXP motifs present in all three proteins. Moreover, viral proteins compete for binding of BS69 to MGA in a PXLXP-dependent fashion. Because deletions in E1A or EBNA2 that cover the PXLXP motifs are non-transforming, our observations suggest a role for BS69 in cell growth control that is reminiscent of abrogation of the Rb function by various oncoproteins.
Ansieau
Stéphane
S
Max Delbrück Center for Molecular Medicine, Robert Rössle Strasse 10, 13092 Berlin, Germany. ansieu@mdc-berlin.de
Leutz
Achim
A
D000256:Adenoviridae / Q000378:metabolism; D017500:Adenovirus E1A Proteins / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001667:Binding, Competitive; D017173:Caenorhabditis elegans / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry* / Q000378:metabolism; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins
D017500:Adenovirus E1A Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D005982:Glutathione Transferase; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C403042:Mga protein, mouse; C094763:ZMYND11 protein, human; C490622:Zmynd11 protein, mouse