Gene Regulation of GATA-4 transcription factor and pathology
| Project/Area Number |
14370744
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
MAEDA Masatomo Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (80190297)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI-OHASHI Ayako Osaka University, Graduate School of Pharmaceutical Sciences, Assistant Professor (Lecturer), 薬学研究科, 講師 (90272484)
|
|---|
| Project Period (FY) |
2002 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2003: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥6,100,000 (Direct Cost: ¥6,100,000)
|
|---|
| Keywords | GATA factor / GATA-4 / GATA-6 / cAMP / transcription factor / translational regulation / cardiac myocyte differentiation / proteolysis / DNA結合蛋白 |
|---|
| Research Abstract |
1.Transcription start sites of GATA-4 gene were not significantly different between rat heart, stomach and testis. In the cardiac myocyte differentiation model (mouse P19.CL6 cells), GATA-4 gene was activated, immediately after induction by DMSO. An E-box and two GC-boxes were important for transcription of GATA-4 gene. However, the -124 bp region with these three boxes was not enough for the induced-expression of reporter gene that was constructed by ligating this 124 bp sequence to the 5'-side of GFP gene. Further upstream -125 〜 -1312 bp region together was required for the induced expression.
2.The cAMP-dependent proteolysis occurred in CHO-K1 cells. The potential phosphorylation site by A-kinase and the PEST sequence on the GATA-6 were not required for the proteolysis, and rather other cellular protein(s) could be a target for A-kinase. Thus it would be of interest to identify novel cellular factor(s) functioning in A-kinase pathway.
3.Two translational isoforms (L- and S-types) were formed from a single mRNA, since additional translational initiation codon was present in frame in the further 5'-upstream region of GATA-6 mRNA being not recognized previously. L-type GATA-6 had extended 146 amino acid residues. The 16-residue region in the L-type specific sequence was required for the extended structure of L-type GATA-6. Furthermore, transcriptional activation potency of L-type GATA-6 was higher. Roles of protein factor(s) interacting with the L-type specific region would be interesting from view points of complex formation and transcriptional regulation.
4.Both L- and S-type GATA-6 were expressed in human cancer cell lines. The growth regulation of such cancer cells through GATA-6 would be next study, since we have now known many molecular properties of GATA-6 in the present research project.
|
Report
(5 results)
Research Products
(19 results)
