Ribosomal stress induces processing of Mybbp1a and its translocation from the nucleolus to the nucleoplasm.

Myb-binding protein 1a (Mybbp1a) was originally identified as a c-myb proto-oncogene product (c-Myb)-interacting protein, and also binds to various other transcription factors. The 160-kDa Mybbp1a protein (p160(MBP)) is ubiquitously expressed and is post-translationally processed in some types of cells to generate an amino-terminal 67 kDa fragment (p67(MBP)). Despite its interaction with various transcription factors, Mybbp1a is localized predominantly, but not exclusively, in nucleoli. Here, we have purified the two Mybbp1a-containing complexes. The smaller complex contained p67(MBP) and p140(MBP), which lacked the C-terminal region of p160(MBP) containing the nucleolar localization sequences. The larger complex contained the intact p160(MBP) and various ribosomal subunits. Treatment of cells with actinomycin D (ActD), cisplatin or UV, all of which inhibit ribosome biogenesis, induced processing of p160(MBP) into p140(MBP) and p67(MBP). ActD, cisplatin and UV also induced a translocation of Mybbp1a from the nucleolus to the nucleoplasm. Both small and large Mybbp1a complexes contained nucleophosmin and nucleolin. In contrast, nucleostemin was detected only in the large complex, while the cell cycle-regulated protein EBP1 was only in the small complex. These results suggest that Mybbp1a may connect the ribosome biogenesis and the Myb-dependent transcription, which controls cell cycle progression and proliferation.