title: The functional and structural characterization of a novel oncogene GIG47 involved in the breast tumorigenesis.
abstract: BACKGROUND
  A candidate oncogene GIG47, previously known as a neudesin with a neurotrophic activity, was identified by applying the differential expression analysis method.
  
  
  METHODS
  As a first step to understand the molecular role of GIG47, we analyzed the expression profile of GIG47 in multiple human cancers including the breast cancer and characterized its function related to human carcinogenesis. Based on this oncogenic role of GIG47, we then embarked on determining the high-resolution structure of GIG47. We have applied multidimensional heteronuclear NMR methods to GIG47.
  
  
  RESULTS
  GIG47 was over-expressed in primary breast tumors as well as other human tumors including carcinomas of the uterine cervix, malignant lymphoma, colon, lung, skin, and leukemia. To establish its role in the pathogenesis of breast cancer in humans, we generated stable transfectants of MCF7 cells. The ectopic expression of GIG47 in MCF7 cells promoted the invasiveness in the presence of 50% serum. In addition, it also resulted in the increased tumorigenicity in in vivo tumor formation assay. The tumorigenesis mechanism involving GIG47 might be mediated by the activation of MAPK and PI3K pathways. These results indicate that GIG47 plays a role in the breast tumorigenesis, thus representing a novel target for the treatment of breast cancer. To facilitate the development of GIG47-targeted therapeutics, we determined the structural configuration of GIG47. The high-resolution structure of GIG47 was obtained by combination of NMR and homology modeling. The overall structure of GIG47 has four α-helices and 6 β-strands, arranged in a β1-α1-β2-β3-α2-β4-α3-α4-β5-β6 topology. There is a potential heme/steroid binding pocket formed between two helices α2 and α3.
  
  
  CONCLUSIONS
  The determined three-dimensional structure of GIG47 may facilitate the development of potential anti-cancer agents.
authors: Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon 305-806, South Korea.
authors: Kyou-Hoon
authors: KH
authors: Han
authors: Si-Hyung
authors: SH
authors: Lee
authors: Seon-Ah
authors: SA
authors: Ha
authors: Hyun Kee
authors: HK
authors: Kim
authors: CheWook
authors: C
authors: Lee
authors: Do-Hyoung
authors: DH
authors: Kim
authors: Kee Hwan
authors: KH
authors: Gong
authors: JinAh
authors: J
authors: Yoo
authors: Sanghee
authors: S
authors: Kim
authors: Jin Woo
authors: JW
authors: Kim
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017433:Protein Structure, Secondary; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C500818:NENF protein, human; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases