Recruitment of TRRAP required for oncogenic transformation by E1A

TRRAP links Myc with histone acetylases and appears to be an important medi ator of its oncogenic function. Here we show that interaction with TRRAP is required for cellular transformation not only by Myc, but also by the aden ovirus EIA protein. Substitution of the 262 N-terminal residues of Myc with a small domain of EIA (residues 12-54) restores Myc transforming function. EIA(12-54) contains a TRRAP-interaction domain, that recruits TRRAP to eit her E1A-Myc chimeras, or the native 12S E1A protein. Overexpression of a co mpeting TRRAP fragment in vivo blocks interaction of cellular TRRAP with ei ther E1A-Myc or EIA, and suppresses cellular transformation by both oncopro teins. Moreover, E1A(Delta 26-35) that fails to bind TRRAP but is capable o f binding the Retinoblastoma (Rb)-family and p300/CBP proteins is defective in cellular immortalization, transformation and cell cycle deregulation. T hus in addition to disrupting Rb and p300/CBP functions, E1A must recruit T RRAP to transform cells.