The COP9 signalosome (CSN) contains eight-subunits and is a highly conserved protein complex implicated in ubiquitin-mediated proteolysis. Jun activation domain-binding protein 1 (Jab1) is the fifth component of CSN (CSN5) with a molecular weight of 38 kDa. Jab1 overexpression is observed in many human cancers, but there is no clear evidence how Jab1 contributes to malignant transformation in human cancers. Bcr-Abl is a cytoplasmic chimeric oncoprotein produced by Philadelphia chromosome
translocation and found in more than 90% of patients with chronic myelogenous leukemia (CML). Recent studies have shown that the Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase and may facilitate cell-cycle progression. In this study, we found that inhibition of Bcr-Abl kinase by STI-571 downregulated 50% of full length human Jab1 promoter activity and gene expression. Promoter deletion assay indicated that the responsive element for Bcr-Abl is located between -405/-223 region of human Jab1 promoter. Treatment of LY294002 also reduced Jab-405/-223 promoter activity and Jab1
expression. Promoter mutagenesis assay and ChIP assay suggest that Bcr-Abl stimulated both £]-catenin /TCF complex and STAT1 bind to the consensus binding sites of Jab-405/-223 promoter. Taken together, Bcr-Abl oncogene may regulate Jab1 via PI3K/AKT signal pathway, £]-catenin /TCF and STAT1 transcription factors.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0816107-112047 |
| Date | 16 August 2007 |
| Creators | Yang, Kuei-Ting |
| Contributors | Hui-Chiu Chang, Yow-Ling Shiue, Wen-Chun Hung |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0816107-112047 |
| Rights | withheld, Copyright information available at source archive |
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