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Research of Human Cancer Associated Gene HCL-G1, Construction, Function and Regulation
Author: ZengWeiQi
Tutor: WuXiuShan;YuanZuoZhou
School: Hunan Normal University
Course: Developmental Biology
Keywords: Lung cancer p53 HCL-G1
CLC: Q78
Type: PhD thesis
Year: 2006
Downloads: 95
Quote: 0
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Abstract
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Cancer is the number one killer of human health, while lung cancer, the highest incidence of cancer. Pathogenesis of lung cancer more than currently known exception occurs due to surface growth factors and growth factor receptors, therefore, further clarify the regulation of receptor downstream gene elucidating the mechanism of the occurrence of lung cancer and further design drug targets are very significance. The study raised the obvious target gene in lung cancer cells - HCL-G1, studied G1 gene and protein structure, identified as a new gene family, the parallel evolution of other genes in the evolution of the highly conserved. The cell positioning results show specificity protein expression in the nucleolus, the demolition segment results show its N-terminal signal peptide does not have a separate function to guide the correct positioning of its protein, and prompted the integrity of the G1 protein for its positioning has important significance. We examined the proliferation of Hela cells G1 overexpression speed the G1 can significantly promote cell proliferation, G1 and cancer relationship, flow cytometry results confirmed the role of the G1 to promote cell proliferation are mainly reflected in accelerated G1- S and G2-M indexable. The western results of display of G1 proliferative effect is not accomplished by adjusting the protein of the cyclin family, which prompted G1 is likely to be through another way to regulate the cell cycle, in a known manner, p53-p21-CDK2 pathway is the most common way of regulating. We use luciferase reporter system analysis of several related signaling pathways and cell proliferation, G1 overexpression significantly inhibited the expression of p53, p21. In order to clarify the relationship between the expression of upstream regulatory factors and G1, we use luciferase reporter system to analyze the promoter region of the G1 and found section of about 601bp promoter sequence carrying G1 G1 80% more than the expression activity. , There are four real MAPK regulation of downstream transcription factor binding sites in the promoter, the E-box, CDE, AP1 and ETS were responsible for the positive and negative regulation of the G1, may also exist in the first 100 bp of the promoter of a suppressing loci to be identified above, MEK1 and MEKK in a complex manner, the precise regulation of the transcription of the G1, EGF, IGF and TGFβ by affecting major kinases in the two-MAPK signaling pathway to complete the regulation of the G1. Known studies have shown that p53 is a cell proliferation, differentiation and apoptosis in a hub, to accept the signal from the cell growth aspects, integrated to determine the fate of the cell, and the G1 cell positioning a strong hint that the cut and rRNA splicing The relationship, therefore, we use the Northern blot analysis of the role of G1 cells of rRNA shear stitching, the results show the G1 downregulated rRNA shear process is also subject to a corresponding inhibition. We use the yeast two-hybrid method identified a G1-interacting protein PES1 homologous proteins in yeast and G1 homologous protein interactions in yeast, and both are located in the nucleolus, PES1 regulation of cell cycle regulation of rRNA shear stitching. Our study eventually shed G1 upstream regulatory mechanism, horizontal role of the protein and its function, and to determine its affect cell cycle through p53-p21-CDK ways, the results prove the occurrence of lung cancer, G1 certainly been unusual upstream growth factor signaling and abnormal expression, an intermediate cancer.
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