Regulation of the nucleus and chromosomes by the ubiquitin-family proteins
| Project/Area Number |
17510166
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied genomics
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
SAITOH Hisato Kumamoto University, Graduate School of Science and Technology, Professor (50211925)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | protein / signaling / biomolecule / development / differentiation / gene / 生物・生体工学 / ユビキチン / SUMO / 翻訳後修飾 |
|---|
| Research Abstract |
SUMOs are small ubiquitin-related modifiers that can covalently attach to target proteins, a process referred to as sumoylation. It has become increasingly clear that a wide variety of cellular proteins can be regulated by sumoylation. It is of interest that, in contrast to ubiquitin, there are at least three SUMO paralogs in human cells, SUMO2, SUMO3 and SUMO1, and SUMO2 and SUMO3 are more related to each other (95% amino acid identity) than they are to SUMO1 (〜50% identity).
In this research project, we first show our current data that indicate quantitative and biochemical distinction between SUMO2/3 and SUMO1 and would like to discuss functional heterogeneity of SUMO2/3 versus SUMO1 in cellular growth and during early development.
We also would like to focus on the role of SUMO2/3 in heterochromatin formation in mammalian cells. We show that human MCAF1 which complexes with methyl-CpG-binding protein MBD1, and SETDB1 that trimethylates histone H3 at lysine 9 (H3-K9) in the presence of MCAF1, both directly bind to SUMO2/3 via short peptide sequences similar to the SUMO-binding motif. We also indicate sumoylation of MBD1 both in vitro and in vivo and demonstrate that modification of MBD1 with SUMO2/3 facilitates an interaction among MBD1, MCAF1 and SETDB1, suggesting that sumoylation links methylation of DNA and histone. In a cultured human cancer cell line, SUMO2/3 are enriched in MBD1 and MCAF1-containing heterochromatin regions that are marked with trimethyl H3-K9 and its binding protein HP1. The specific knockdown of SUMO2/3 induces the dissociation of MCAF1, trimethyl H3-K9, and HP1 from the MBD1-containing heterochromatin foci, suggesting the requirement of SUMO2/3 for assembly of the heterochromatin proteins. These findings imply SUMO2/3's function as an epigenetic modulator for heterochromatin formation, at least in part, via regulating MCAF1-SETDB1-MBD1 interaction.
|
Report
(3 results)
Research Products
(17 results)
