REGULATION OF THE ETS-RELATED TRANSCRIPTION FACTOR ELF-1 BY BINDING TO THE RETINOBLASTOMA PROTEIN

The retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets tra nscription factor that regulates inducible gene expression during T ce ll activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of sev eral viral oncoproteins and binds to the pocket region of Rb both in v itro and in vivo. Elf-1 binds exclusively to the underphosphorylated f orm of Rb and fails to bind to Rb mutants derived from patients with r etinoblastoma. Co-immunoprecipitation experiments demonstrated an asso ciation between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of E lf-1, which is correlated temporally with the activation of Elf-1-medi ated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1-dependent transcription during T cell activatio n. These results demonstrate that Rb interacts specifically with a lin eage-restricted Ets transcription factor. This regulated interaction m ay be important for the coordination of lineage-specific effector func tions such as lymphokine production with cell cycle progression in act ivated T cells.