JCB logo
Keystone Symposia
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online April 9, 2007
doi:10.1083/jcb.200611036
The Journal of Cell Biology, Vol. 177, No. 1, 51-61
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Tuvia et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tuvia, S.
Right arrow Articles by Reiss, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tuvia, S.
Right arrow Articles by Reiss, Y.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp

Shmuel Tuvia, Daniel Taglicht, Omri Erez, Iris Alroy, Iris Alchanati, Vivian Bicoviski, Mally Dori-Bachash, Danny Ben-Avraham, and Yuval Reiss

Proteologics Ltd., Kiryat Weizmann, Rehovot 76124, Israel

Correspondence to Yuval Reiss: yuval{at}proteologics.com

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.

S. Tuvia's present address is Bioline Innovations Jerusalem, Jerusalem 91450, Israel.

I. Alroy's present address is Pharmos Ltd., Kiryat Weizmann, Rehovot 76326, Israel.

M. Dori-Bachash's present address is Dept. of Plant Pathology and Microbiology, Faculty of Agricultural, Food, and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel.

Abbreviations used in this paper: AMFR, autocrine motility factor receptor; CHX, cycloheximide; ERAD, ER-associated degradation; MBP, maltose-binding protein; NRIF, neurotrophin receptor–interacting factor; shRNA, small hairpin RNA; tHerp, truncated Herp; Tm, tunicamycin; Tpg, thapsigargin; TRAF, TNF receptor–associated factor; Ub, ubiquitin.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents