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© The Rockefeller University Press, 0021-9525/1999//823 $5.00
The Journal of Cell Biology, Volume 144, Number 5, , 1999 823-838

The β4 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 β4 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 β4 integrin, p27^BBP/eIF6 is present in the cytoplasm and enriched at hemidesmosomes with a pattern similar to that of β4 integrin. Surprisingly, in the absence and in the presence of the β4 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 β4 integrin subunit may have evolved specifically in higher eukaryotic cells.

Key Words: epithelial cells • yeast • nucleolus • hemidesmosomes • intermediate filaments

Abbreviations used in this paper: BBP, beta4 binding protein; ECL, chemiluminescence detection system; eIF, eukaryotic (translation) initiation factor; HA, hemagglutinin; IIH, integrin interacting homologue.

Address correspondence to Stefano Biffo, Lab. Istologia Molecolare DIBIT, San Raffaele Scientific Institute, V. Olgettina 58, 20132 Milano, Italy. Tel.: 39-22-643-4857. Fax: 39-22-643-4855. E-mail: s.biffo{at}hsr.it

The financial support of Telethon-Italy (grant 762 and E.712) is gratefully acknowledged. The work was supported also by Associazione Italiana per la Ricerca sul Cancro, Giovanni Armenise-Harvard Foundation, and MURST to P.C. Marchisio, and by CNR Target Project on Biotechnology Grant CT.97.01180.PF49(F).

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