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Science 28 May 1993:
Vol. 260. no. 5112, pp. 1330 - 1335
DOI: 10.1126/science.8493578
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Articles

Science, Vol 260, Issue 5112, 1330-1335
Copyright © 1993 by American Association for the Advancement of Science

articles

Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein

CY Wang, B Petryniak, CB Thompson, WG Kaelin, and JM Leiden

Department of Medicine, University of Chicago, IL 60637.

The retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1-dependent transcription during T cell activation. These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor. This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells.


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