| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2012: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
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| Outline of Final Research Achievements |
Polyglutamine diseases are caused by cytosine-adenine-guanine (CAG) trinucleotide expansions that are translated to a polyglutamine (pQ) chain in specific genes. This pQ chains tend to destabilize the entire proteins making them aggregate. The aggregates are especially toxic in the nucleus for a variety of reasons. Thus, for treating pQ diseases, targeting the nuclear pQ aggregates for degradation seems to be a promising approach. The nuclear ubiquitin proteasome system is the only major protein degradation machinery in the nucleus since the autophagy lysosome system, cannot function in the nucleus. We found that ubiquitin ligase UHRF2 recognizes and promotes nuclear pQ degradation, thus activation of these ubiquitin ligases could be one of the therapeutic approaches. In addition, we also found that one of the histone deacetylases (HDAC), HDAC3, regulates the nuclear ubiquitin proteasome system.
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