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Identification of nerve growth factor-responsive element of the TCL1 promoter as a novel negative regulatory element.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hiromura, Makoto Suizu, Futoshi Narita, Masumi Kinowaki, Keiichi Noguchi, Masayuki |
| Copyright Year | 2006 |
| Abstract | The serine/threonine kinase, Akt (protein kinase B) plays a central role in the regulation of intracellular cell survival. Recently, we demonstrated that the proto-oncogene TCL1, overexpressed in human T-cell prolymphocytic leukemia, is an Akt kinase co-activator. Tightly restricted TCL1 gene expression in early developmental cells suggested that the TCL1 gene is regulated at a transcriptional level. To characterize how TCL1 gene expression is regulated, we cloned the 5'-promoter of the TCL1 gene located at human chromosome 14q32. The 5'-TCL1 promoter region contains a TATA box with cis-regulatory elements for Nur77/NGFI-B (nerve growth factor-responsive element (NBRE), CCAAGGTCA), NFkappaB, and fork head transcription factor. Nur77/NGFI-B, an orphan receptor superfamily transcription factor implicated in T-cell apoptosis, is a substrate for Akt. We hypothesized that TCL1 transactivity is regulated through Akt-induced phosphorylation of Nur77/NGFI-B in vivo. In an electrophoretic mobility shift assay with chromosomal immunoprecipitation assays, wild-type Nur77, but not S350A mutant Nur77, could specifically bind to TCL1-NBRE. A luciferase assay demonstrated that TCL1-NBRE is required for inhibition of TCL1 transactivity upon nerve growth factor/platelet-derived growth factor stimulation, which activates Akt and phosphorylates Nur77. Using a chromosomal immunoprecipitation assay with reverse transcription-PCR, nerve growth factor stimulation inhibited binding of endogenous Nur77 to TCL1-NBRE, in turn, suppressing TCL1 gene expression. The results together establish that TCL1-NBRE is a novel negative regulatory element of Nur77 (NGFI-B). To the best of our knowledge, TCL1-NBRE is the first direct target of Nur77 involving the regulation of intracellular cell death survival. This Akt-induced inhibitory mechanism of TCL1 should play an important role in immunological and/or neuronal development in vivo. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/14759/1/JBC281-38.pdf |
| Alternate Webpage(s) | http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/14759/1/JBC281-38.pdf |
| PubMed reference number | 16835233v1 |
| Volume Number | 281 |
| Issue Number | 38 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 14q32 Apoptosis Blood Platelets Cell Death Cell Survival Clone Cells Gene Expression HMGN2 Protein Luciferases MARK2 gene Oncogenes Platelet-Derived Growth Factor Promoter Regions, Genetic Protein Kinases Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Proto-Oncogenes Regulatory Sequences, Nucleic Acid Reverse Transcription T-Cell Prolymphocytic Leukemia T-Lymphocyte TATA Box TCL1A gene TCL1A wt Allele TRANSCRIPTION FACTOR Threonine Transcription, Genetic |
| Content Type | Text |
| Resource Type | Article |
