The Structure and Biological Function of CREG
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Authors: Ghobrial, Gaby; Araujo, Luiz; Jinwala, Felecia; Li, Shaohua; Lee, Leonard Y.
Abstract
The cellular repressor of E1A-stimulated genes (CREG) is a 220 amino acid glycoprotein structurally similar to oxidoreductases. However, CREG does not have enzymatic activities because it cannot bind to the cofactor flavin mononucleotide. Although CREG can be secreted, it is mainly an intracellular protein localized in the endocytic-lysosomal compartment. It undergoes proteolytic maturation mediated by lysosomal cysteine proteases. Biochemical studies have demonstrated that CREG interacts with mannose-6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R) and exocyst Sec8. CREG inhibits proliferation and induces differentiation and senescence when overexpressed in cultured cells. In Drosophila, RNAi-mediated knockdown of CREG causes developmental lethality at the pupal stage. In mice, global deletion of the CREG1 gene leads to early embryonic death. These findings establish an essential role for CREG in development. CREG1 haploinsufficient and liver-specific knockout mice are susceptible to high fat diet-induced obesity, hepatic steatosis and insulin resistance. The purpose of this review is to provide an overview of what we know about the biochemistry and biology of CREG and to discuss the important questions that remain to be addressed in the future.
Transcriptomic basis of neutrophil ratio variation induced by poly I:C stimulation in porcine peripheral blood
FRONTIERS OF AGRICULTURAL SCIENCE AND ENGINEERING
Authors: Wang, Haiyan; Zhang, Qiaoxia; Yin, Lilin; Liu, Xiangdong; Zhao, Shuhong; Zhu, Mengjin; Li, Changchun
Abstract
Neutrophils are vital components of defense mechanisms against invading pathogens and are closely linked with the individual antiviral capacity of pigs and other mammals. Neutrophilia is a well-known clinical characteristic of viral and bacterial infections. Using Affymetrix porcine genome microarrays, we investigated the gene expression profiles associated with neutrophil variation in porcine peripheral blood before and after polyriboinosinic-polyribocytidylic acid stimulation. Transcriptomic analysis showed 796 differentially expressed genes (DEGs) in extreme response (ER) pigs and 192 DEGs in moderate response (MR) pigs. Most DEGs were related to immune responses, included MXD1, CXCR4, CREG1, MyD88, CD14, TLR2, TLR4, IRF3 and IRF7. Gene ontology analysis indicated that the DEGs of both ER and MR pigs were involved in common biological processes, such as cell proliferation, growth regulation, immune response, inflammatory response and cell activation. The ER and MR groups also showed differences in DEGs involved in biological processes. DEGs involved in cell division and cell cycle were specifically found in the ER pigs, whereas DEGs involved in cell migration were specifically found in the MR pigs. The study provides a basic understanding of the molecular basis for the antiviral capacity of pigs and other mammals.