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First published online July 12, 2005
doi: 10.1242/10.1242/jcs.02452

Journal of Cell Science 118, 3185-3194 (2005)
Published by The Company of Biologists 2005
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Research Article

HOPS: a novel cAMP-dependent shuttling protein involved in protein synthesis regulation

Maria Agnese Della Fazia, Marilena Castelli, Daniela Bartoli, Stefania Pieroni, Valentina Pettirossi, Danilo Piobbico, Mariapia Viola-Magni and Giuseppe Servillo*

Department of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, 06122 Perugia, Italy

* Author for correspondence (e-mail: labiomol{at}unipg.it)

Accepted 21 April 2005

The liver has the ability to autonomously regulate growth and mass. Following partial hepatectomy, hormones, growth factors, cytokines and their coupled signal transduction pathways have been implicated in hepatocyte proliferation. To understand the mechanisms responsible for the proliferative response, we studied liver regeneration by characterization of novel genes that are activated in residual hepatocytes. A regenerating liver cDNA library screening was performed with cDNA-subtracted probes derived from regenerating and normal liver. Here, we describe the biology of Hops (for hepatocyte odd protein shuttling). HOPS is a novel shuttling protein that contains an ubiquitin-like domain, a putative NES and a proline-rich region. HOPS is rapidly exported from the nucleus and is overexpressed during liver regeneration. Evidence shows that cAMP governs HOPS export in hepatocytes of normal and regenerating liver and is mediated via CRM-1. We demonstrate that HOPS binds to elongation factor eEF-1A and interferes in protein synthesis. HOPS overexpression in H-35-hepatoma and 3T3-NIH cells strongly reduces proliferation.

Key words: shuttling protein, proliferation, liver, eEF-1A, hepatoma cells, liver regeneration


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© The Company of Biologists Ltd 2005