HOPS: a novel cAMP-dependent shuttling protein involved in protein synthesis regulation
HOPS: a novel cAMP-dependent shuttling protein involved in protein synthesis regulation
复制标题
DOI：
10.1242/jcs.02452
复制
发表时间：
2005-07-15
影响因子：
4
通讯作者：
Servillo, G
中科院分区：
文献类型：
--
作者：
Della Fazia, MA;Castelli, M;Servillo, G
肝脏有自主调节生长和质量的能力。肝部分切除术后，激素、生长因子、细胞因子及其耦合信号转导通路与肝细胞增殖有关。为了了解负责增殖反应的机制，我们通过表征残留肝细胞中激活的新基因来研究肝再生。用再生肝脏和正常肝脏的dna减去探针进行再生肝脏cDNA文库筛选。在这里，我们描述了啤酒花（用于肝细胞奇蛋白穿梭）的生物学。啤酒花是一种新型的穿梭蛋白，它包含一个泛素样结构域，一个假定的NES和一个富含脯氨酸的区域。啤酒花从细胞核迅速输出，并在肝脏再生过程中过度表达。有证据表明，cAMP控制正常肝细胞和再生肝细胞的HOPS输出，并通过CRM-1介导。我们证明了啤酒花结合延伸因子eEF-1A并干扰蛋白质合成。h -35肝癌细胞和3T3-NlH细胞过表达啤酒花可显著抑制细胞增殖。
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-NlH cells strongly reduces proliferation.