| Budget Amount *help |
¥82,810,000 (Direct Cost: ¥63,700,000、Indirect Cost: ¥19,110,000)
Fiscal Year 2016: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2015: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2014: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2013: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2012: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000)
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| Outline of Final Research Achievements |
Most of transmembrane proteins are integrated into the ER by virtue of a signal sequence-mediated co-translational process. However, a substantial portion of transmembrane proteins fail to access the ER, resulting in the production of cytosolically mislocalized polypeptides. Their appropriate recognition and removal are of the utmost significance to avoid potential proteotoxic stress. Here, we identified UBA domain protein UBQLN4 for the elimination of such newly synthesized defective polypeptides. Using a model transmembrane domain protein whose degradation occurs at a pre-ER incorporation process, we show that UBQLN4 recognizes misassembled proteins in the cytoplasm for targeting to the proteasome pathway. Importantly, UBQLN4 recognized not only the model defective transmembrane substrate but also a pool of endogenous defective proteins that were induced by compromising the signal recognition particle.
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