The beta 4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly

p27(BBP/eIF6) is an evolutionarily conserved protein that was originally id entified as p27(BBP), an interactor of the cytoplasmic domain of integrin b eta 4 and, independently, as the putative translation initiation factor eIF 6. To establish the in vivo function of p27(BBP/eIF6), its topographical di stribution was investigated in mammalian cells and the effects of disruptin g the corresponding gene was studied in the budding yeast, Saccharomyces ce revisiae. In epithelial cells containing beta 4 integrin, p27(BBP/eIF6) is present in the cytoplasm and enriched at hemidesmosomes with a pattern simi lar to that of beta 4 integrin. Surprisingly, in the absence and in the pre sence of the beta 4 integrin subunit, p27(BBP/eIF6) is in the nucleolus and associated with the nuclear matrix. Deletion of the IIH S. cerevisiae gene , encoding the yeast p27(BBP/eIF6) homologue, is lethal, and depletion of t he corresponding gene product is associated with a dramatic decrease of the level of free ribosomal 60S subunit. Furthermore, human p27(BBP/eIF6) can rescue the lethal effect of the iih Delta yeast mutation. The data obtained in vivo suggest an evolutionarily conserved function of p27(BBP/eIF6) is r ibosome biogenesis or assembly rather than in translation. A further functi on related to the beta 4 integrin subunit may have evolved specifically in higher eukaryotic cells.