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The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp
| Content Provider | Scilit |
|---|---|
| Author | Tuvia, Shmuel Taglicht, Daniel Erez, Omri Alroy, Iris Alchanati, Iris Bicoviski, Vivian Dori-Bachash, Mally Ben-Avraham, Danny Reiss, Yuval |
| Copyright Year | 2007 |
| Description | The ubiquitin (Ub) domain protein Herp plays a crucial role in the maintenance of calcium homeostasis during endoplasmic reticulum (ER) stress. We now show that Herp is a substrate as well as an activator of the E3 Ub ligase POSH. Herp-mediated POSH activation requires the Ubl domain and exclusively promotes lysine-63–linked polyubiquitination. Confocal microscopy demonstrates that Herp resides mostly in the trans-Golgi network, but, shortly after calcium perturbation by thapsigargin (Tpg), it appears mainly in the ER. Substitution of all lysine residues within the Ubl domain abolishes lysine-63–linked polyubiquitination of Herp in vitro and calcium-induced Herp relocalization that is also abrogated by the overexpression of a dominant-negative POSHV14A. A correlation exists between the kinetics of Tpg-induced Herp relocalization and POSH-dependent polyubiquitination. Finally, the overexpression of POSH attenuates, whereas the inhibition of POSH by the expression of POSHV14A or by RNA interference enhances Tpg-induced calcium burst. Altogether, these results establish a critical role for POSH-mediated ubiquitination in the maintenance of calcium homeostasis through the spatial control of Herp. |
| Related Links | http://jcb.rupress.org/content/jcb/177/1/51.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064109/pdf |
| Ending Page | 61 |
| Page Count | 11 |
| Starting Page | 51 |
| DOI | 10.1083/jcb.200611036 |
| Journal | Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 177 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2007-04-09 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Calcium Homeostasis Journal: Journal of Cell Biology (Vol- 177, Issue- 1) |
| Content Type | Text |