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Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression.

Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.

ABSTRACT

Studies of naturally occurring mutations of the RB1 tumor suppressor gene have indicated that the E1A/T antigen-binding domain is important for pRb function. Mutations engineered within the C-terminal 135 amino acids of pRb also abrogate its growth-suppressive function during the G1 interval of the cell cycle. Both the pRb E1A/T antigen-binding domain and the C-terminal domain are required for interaction with the E2F transcription factor. A series of mutated pRb proteins has been used to define the C-terminal sequences which determine E2F binding, adenovirus E2 promoter inhibition, and negative growth control. Deletion of the C terminus to residue 870 allowed full pRb function, while further deletion to residue 841 inactivated pRb in each assay. Amino acid sequences immediately C-terminal to the E1A/T antigen-binding domain were absolutely required for pRb activity. Mutations which prevented pRb from interacting with E2F also eliminated pRb-mediated E2 promoter repression and inactivated the ability of pRb to suppress cell growth.

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