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The Partial Homeodomain of the Transcription Factor Pax-5 (BSAP) Is an Interaction Motif for the Retinoblastoma and TATA-binding Proteins¹

Research Institute of Molecular Pathology, A-1030 Vienna, Austria

² To whom requests for reprints should be addressed, at Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria. Phone: 43-1-797-30-884; Fax: 43-1-798-71-53; E-mail: busslinger{at}nt.imp.univie.ac.at.

Pax-5 codes for the transcription factor BSAP, which plays an important role in midbrain patterning, B cell development, and lymphoma formation. Pax-5 is known to control gene expression by recognizing its target genes via the NH₂-terminal paired domain and by regulating transcription through a COOH-terminal regulatory module consisting of activating and inhibitory sequences. The central region of Pax-5 contains a sequence with significant homology to the first -helix of the paired-type homeodomain. This partial homeodomain has been highly conserved throughout vertebrate evolution because it is found not only in Pax-5 but also in the related Pax-2 and Pax-8 members of the same Pax subfamily. Here we report that the partial homeodomain binds the TATA-binding protein (TBP) and retinoblastoma (Rb) gene product. Both TBP and Rb were shown by coimmunoprecipitation experiments to directly associate with Pax-5 in vivo. The conserved core domain of TBP and the pocket region as well as COOH-terminal sequences of Rb are required for interaction with the partial homeodomain of Pax-5 in in vitro binding assays. Furthermore, Pax-5 was specifically bound only by the underphosphorylated form of Rb. These data indicate that Pax-5 is able to contact the basal transcription machinery through the TBP-containing initiation factor TFIID, and that its activity can be controlled by the cell cycle-regulated association with Rb.

¹ Contributed as part of the April 1, 1999 Supplement to Cancer Research, "General Motors Cancer Research Foundation Twentieth Annual Scientific Conference: Developmental Biology and Cancer." This work was supported in part by a Grant from the Austrian Industrial Research Promotion Fund. D. E. was the recipient of a fellowship from the Deutsche Forschungsgemeinschaft and European Community.

Received 9/18/98. Accepted 2/ 1/99.