J. Cell Biol., Volume 144, Number 5, March 8, 1999 823-838

The 4 Integrin Interactor p27^BBP/eIF6 Is an Essential Nuclear Matrix Protein Involved in 60S Ribosomal Subunit Assembly

Francesca Sanvito,^* Simonetta Piatti,^§ Antonello Villa,^* Mario Bossi,^* Giovanna Lucchini,^§ Pier Carlo Marchisio,^*¶ and Stefano Biffo^*

^* DIBIT, Department of Biological and Technological Research, and  Department of Pathology, San Raffaele Scientific Institute, 20132 Milano, Italy; ^§ Dipartimento di Genetica e di Biologia dei Microrganismi, University of Milano, 20133 Milano, Italy;  Department of Pharmacology, University of Milano and CNR Center, 20129 Milano, Italy; and ^¶ Department of Biomedical Sciences and Human Oncology, University of Torino School of Medicine, 10126 Torino, Italy

p27^BBP/eIF6 is an evolutionarily conserved protein that was originally identified as p27^BBP, an interactor of the cytoplasmic domain of integrin 4 and, independently, as the putative translation initiation factor eIF6. To establish the in vivo function of p27^BBP/eIF6, its topographical distribution was investigated in mammalian cells and the effects of disrupting the corresponding gene was studied in the budding yeast, Saccharomyces cerevisiae. In epithelial cells containing 4 integrin, p27^BBP/eIF6 is present in the cytoplasm and enriched at hemidesmosomes with a pattern similar to that of 4 integrin. Surprisingly, in the absence and in the presence of the 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 the 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 yeast mutation. The data obtained in vivo suggest an evolutionarily conserved function of p27^BBP/eIF6 in ribosome biogenesis or assembly rather than in translation. A further function related to the 4 integrin subunit may have evolved specifically in higher eukaryotic cells.

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