Recruitment of TRRAP required for oncogenic transformation by E1A.
TRRAP links Myc with histone acetylases and appears to be an important mediator of its oncogenic function. Here we show that interaction with TRRAP is required for cellular transformation not only by Myc, but also by the adenovirus E1A protein. Substitution of the 262 N-terminal residues of Myc with a small domain of E1A (residues 12-54) restores Myc transforming function. E1A(12-54) contains a TRRAP-interaction domain, that recruits TRRAP to either E1A-Myc chimeras, or the native 12S E1A protein. Overexpression of a competing TRRAP fragment in vivo blocks interaction of cellular TRRAP with either E1A-Myc or E1A, and suppresses cellular transformation by both oncoproteins. Moreover, E1A(Delta26-35) that fails to bind TRRAP but is capable of binding the Retinoblastoma (Rb)-family and p300/CBP proteins is defective in cellular immortalization, transformation and cell cycle deregulation. Thus in addition to disrupting Rb and p300/CBP functions, E1A must recruit TRRAP to transform cells.
Deleu
L
L
Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Shellard
S
S
Alevizopoulos
K
K
Amati
B
B
Land
H
H
D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019943:Amino Acid Substitution; D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; C113829:transformation-transcription domain-associated protein