The functional and structural characterization of a novel oncogene GIG47 involved in the breast tumorigenesis

Cited 14 time in scopus
Metadata Downloads
Title
The functional and structural characterization of a novel oncogene GIG47 involved in the breast tumorigenesis
Author(s)
Kyou Hoon Han; Si Hyoung Lee; S A Ha; H K Kim; Chewook Lee; Do Hyoung Kim; K H Gong; J Yoo; S Kim; J W Kim
Bibliographic Citation
BMC Cancer, vol. 12, pp. 274-274
Publication Year
2012
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.Conclusion: The determined three-dimensional structure of GIG47 may facilitate the development of potential anti-cancer agents.
Keyword
Anti-cancer agentsBreast cancerGig47OncogeneThree-dimensional structure
ISSN
1471-2407
Publisher
Springer-BMC
DOI
http://dx.doi.org/10.1186/1471-2407-12-274
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > Core Facility Management Center > 1. Journal Articles
Files in This Item:

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.