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

Abstract

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.

MicroRNA miR-27 Inhibits Adenovirus Infection by Suppressing the Expression of SNAP25 and TXN2

“…2C). TMUB1 (also known as HOPS) and TMBIM6 (also known as TEGT or BI-1) are genes associated with translational regulation and apoptosis, respectively (50,51). It would be interesting to examine whether these genes are involved in the regulation of Ad infection.…”

Different functions of HOPS isoforms in the cell

“…1 Either cAMP or EGF can delocalize HOPS from nucleus to cytoplasm in hepatocytes, in a few minutes of in vitro or in vivo treatment. HOPS export is dependent on CRM-1 activity.…”

“…3,4 Cells treated with Leptomycin B accumulate HOPS in the nucleus. 1,5 Indeed, HOPS has been identified in cytoplasmic complexes as binding a number of centrosomal proteins that are supposedly centrosomal precursors. 6 HOPS knockdown causes centrosome alteration with hyperamplification and multinucleated cells, and the formation of micronuclei.…”

“…1 Polyclonal PG105 antibody was generated as previously described. 1 The serum of 2 rabbits was collected and immunopurified on a column Sulfo-Link coupling gel (Pierce), where the specific peptide had been immobilized.…”

“…1 Polyclonal PG105 antibody was generated as previously described. 1 The serum of 2 rabbits was collected and immunopurified on a column Sulfo-Link coupling gel (Pierce), where the specific peptide had been immobilized. To test the specificity of the antibody, a quenching test was performed with different amounts of the specific peptide in western blot (WB) and in immunohistochemistry analyses.…”