MOLECULAR-CLONING REVEALS THAT THE P160 MYB-BINDING PROTEIN IS A NOVEL, PREDOMINANTLY NUCLEOLAR PROTEIN WHICH MAY PLAY A ROLE IN TRANSACTIVATION BY MYB

We have previously detected two related murine nuclear proteins, p160 and p67, that can bind to the leucine zipper motif within the negative regulatory domain of the Myb transcription factor. We now describe th e molecular cloning of cDNA corresponding to murine p160. The P160 gen e is located on mouse chromosome 11, and related sequences are found o n chromosomes 1 and 12. The predicted p160 protein is novel, and in ag reement with previous studies, we find that the corresponding 4.5-kb m RNA is ubiquitously expressed. We showed that p67 is an N-terminal fra gment of p160 which is generated by proteolytic cleavage in certain ce ll types. The protein encoded by the cloned p160 cDNA and an engineere d protein (p67) comprising the amino-terminal region of p160 exhibit binding specificities for the Myb and Jun leucine zipper regions ident ical to those of endogenous p160 and p67, respectively. This implies t hat the Myb-binding site of p160 lies within the N-terminal 580 residu es and that the Jun-binding site is C-terminal to this position. Moreo ver, we show that p67 but not p160 can inhibit transactivation by Myb . Unexpectedly, immunofluorescence studies show that p160 is localized predominantly in the nucleolus. The implications of these results for possible functions of p160 are discussed.