2014 Fiscal Year Final Research Report
Identification of cascade factor that stimulates dephosphorylation of transcription factor Sp1 by dioxin
| Project/Area Number |
24510081
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Risk sciences of radiation/Chemicals
|
|---|
| Research Institution | Hirosaki University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | ダイオキシン / ダイオキシン受容体 / Sp1 / PP2A / リン酸化 |
|---|
| Outline of Final Research Achievements |
We used a site-specific phospho-antibody to show that treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole (OP) reduced the level of pSer-59 in Sp1 from HepG2 cells. This reduction was too much, we hypothesized that the reduced phosphorylation level resulted from activation of phosphatase activity. Given that pSer-59 is dephosphorylated by PP2A, we examined the effect of a PP2A inhibitor, okadaic acid (OA), on pSer-59 and transcription of CYP1A1. The results showed that OA blocked dephosphorylation of Ser-59 and drastically inhibited transcription of CYP1A1. Similar results were obtained after knockdown of PP2A. Treatment with OA had no effect on the expression of AhR, its nuclear translocation, or its ability to bind to the XRE. Furthermore, dephosphorylation of Sp1 at Ser-59 was not affected by knockdown of AhR. These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription.
|
| Free Research Field |
分子生物学
|
