Nuclear localization conferred by the pocket domain of the retinoblastoma gene product

The tumor suppressor Rb is a nuclear phosphoprotein that controls cell grow th and differentiation by modulating the activity of certain transcription factors. Transport of Rb to the nucleus is affected by both a bipartite nuc lear localization signal (NLS) in the C-terminus of the protein and a centr al domain, termed A/B or pocket, through which Rb interacts with transcript ion factors and viral oncoproteins. Mutations in either the A or B subdomai ns of the pocket render a NLS-deficient Rb completely cytoplasmic. Fusing t he A/B domain of Rb to the Escherichia coil P-galactosidase, to create beta gal-A/B, confers nuclear localization upon this bacterial protein. Moreove r, co-expression with the adenovirus oncoprotein, EIA, further augments nuc lear localization of beta gal-A/B. These findings provide direct evidence t hat the pocket domain of Rb is not only required but also sufficient to ind uce nuclear transport by a 'piggyback' mechanism. Thus, nuclear localizatio n of Rb is dictated by two independent and autonomous domains: (i) the bipa rtite NLS and (ii) the pocket domain. We suggest that via these domains, Rb chaperons and co-compartmentalizes with its associated factors and preempt s their activity prior to nuclear transport. (C) 1999 Elsevier Science B.V. All rights reserved.