| First Author | Marutani T | Year | 2011 |
| Journal | Biochim Biophys Acta | Volume | 1810 |
| Issue | 8 | Pages | 790-8 |
| PubMed ID | 21600962 | Mgi Jnum | J:177751 |
| Mgi Id | MGI:5295927 | Doi | 10.1016/j.bbagen.2011.04.017 |
| Citation | Marutani T, et al. (2011) ER-stress-inducible Herp, facilitates the degradation of immature nicastrin. Biochim Biophys Acta 1810(8):790-8 |
| abstractText | BACKGROUND: Herp is an endoplasmic reticulum (ER)-stress-inducible membrane protein harboring an ubiquitin-like domain (ULD). However, its biological functions are not fully understood. Here, we examined the role of Herp in the degradation of gamma-secretase components. METHODS: Effects of ULD-lacking Herp (DeltaUb-Herp) expression on the degradation of gamma-secretase components were analyzed. RESULTS: The cellular expression of DeltaUb-Herp was found to inhibit the degradation of overexpressed immature nicastrin and full-length presenilin. The mechanisms underlying Herp-mediated nicastrin degradation was further analyzed. We found that immature nicastrin accumulates in the ER of DeltaUb-Herp overexpressing cells or Herp-deficient cells more than that in the ER of wild-type cells. Further, DeltaUb-Herp expression inhibited nicastrin ubiquitination, suggesting that the ULD of Herp is likely involved in nicastrin ubiquitination. Co-immunoprecipitation study showed that Herp as well as DeltaUb-Herp potentially interacts with nicastrin, mediating nicastrin interaction with p97, which functions in retranslocation of misfolded proteins from the ER to the cytosol. CONCLUSIONS: Thus, Herp is likely involved in degradation of immature nicastrin by facilitating p97-dependent nicastrin retranslocation and ubiquitination. General significance: We suggest that Herp could play a role in the elimination of the excess unassembled components of a multimeric complex. |
