| Project/Area Number |
15603004
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
細胞死(アポトーシス)
|
|---|
| Research Institution | Sapporo Medical University |
|---|
Principal Investigator |
ADACHI Masaaki SAPPORO MEDICAL UNIVERSITY, FIRST DEPARTMENT OF INTERNAL MEDICINE, ASSOCIATE PROF., 医学部, 助教授 (70240926)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IMAI Kohzoh SAPPORO MEDICAL UNIVERSITY, PRESIDENT., 学長 (60117603)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | BH-3 only protein / apoptosis / mitochondria / phosphorylation / TOF-Mass / chaperone / BH3-only蛋白 / Akt / アノイキス |
|---|
| Research Abstract |
Most Bcl-2 family members are targeted to the mitochondria through their carboxyl terminal hydrophobic domain. A pro-apoptotic B113-only protein BAD is targeted to the mitochondria, although it has no hydrophobic tail. Mitochondrial translocation is believed to be a crucial event of BAD-mediated apoptosis, but the targeting mechanism is less clear. In this project, we demonstrate that intracellular localization of extrinsic GFP-BAD varied in transfected cell lines, i.e., cytoplasmic localization or mitochondrial accumulation. Interestingly, though GFP-BAD was dispersed throughout the cytoplasm and the nucleus, co-transfection with Bcl-xL recruited it to the mitochondria without any apoptotic signals. In contrast, co-transfection of GFP-BAD with the mutant Bcl-xL lacking hydrophobic c-terminus (Bcl-xLΔC) could not recruit BAD to the mitochondria. TOF-mass analysis of BAD-associating proteins fished Bcl-xL and 14-3-3 abundantly. Importantly, endogeneous BAD proteins mostly retained at the mitochondria in human oral squamous cell carcinoma SAS cells, and that was firmly interfered by the Bcl-xLΔC overexpression. These data indicate that Bcl-xL can recruit BAD to the mitochondria, and this process appears to occur independently of apoptotic signals.
|
