JAMP optimizes ERAD to protect cells from unfolded proteins

Marianna Tcherpakov, Limor Broday, Agnes Delaunay, Takayuki Kadoya, Ashwani Khurana, Hediye Erdjument-Bromage, Paul Tempst, Xiao Bo Qiu, George N. Demartino, Zéev Ronai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Clearance of misfolded proteins from the ER is central for maintenance of cellular homeostasis. This process requires coordinated recognition, ER-cytosol translocation, and finally ubiquitination-dependent proteasomal degradation. Here, we identify an ER resident seven-transmembrane protein (jAMP) that links ER chaperones, channel proteins, ubiquitin ligases, and 26S proteasome subunits, thereby optimizing degradation of misfolded proteins. Elevated JAMP expression promotes localization of proteasomes at the ER, with a concomitant effect on degradation of specific ER-resident misfolded proteins, whereas inhibiting JAMP promotes the opposite response. Correspondingly, a jamp-1 deleted Caenorhabditis elegans strain exhibits hypersensitivity to ER stress and increased UPR. Using biochemical and genetic approaches, we identify JAMP as important component for coordinated clearance of misfolded proteins from the ER.

Original languageEnglish (US)
Pages (from-to)5019-5028
Number of pages10
JournalMolecular Biology of the Cell
Volume19
Issue number11
DOIs
StatePublished - Nov 2008

Fingerprint

Protein Unfolding
Proteins
Ubiquitin-Protein Ligases
Ubiquitination
Caenorhabditis elegans
Proteasome Endopeptidase Complex
Cytosol
Proteolysis
Molecular Biology
Hypersensitivity
Homeostasis
Maintenance

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Tcherpakov, M., Broday, L., Delaunay, A., Kadoya, T., Khurana, A., Erdjument-Bromage, H., ... Ronai, Z. (2008). JAMP optimizes ERAD to protect cells from unfolded proteins. Molecular Biology of the Cell, 19(11), 5019-5028. https://doi.org/10.1091/mbc.E08-08-0839

JAMP optimizes ERAD to protect cells from unfolded proteins. / Tcherpakov, Marianna; Broday, Limor; Delaunay, Agnes; Kadoya, Takayuki; Khurana, Ashwani; Erdjument-Bromage, Hediye; Tempst, Paul; Qiu, Xiao Bo; Demartino, George N.; Ronai, Zéev.

In: Molecular Biology of the Cell, Vol. 19, No. 11, 11.2008, p. 5019-5028.

Research output: Contribution to journalArticle

Tcherpakov, M, Broday, L, Delaunay, A, Kadoya, T, Khurana, A, Erdjument-Bromage, H, Tempst, P, Qiu, XB, Demartino, GN & Ronai, Z 2008, 'JAMP optimizes ERAD to protect cells from unfolded proteins', Molecular Biology of the Cell, vol. 19, no. 11, pp. 5019-5028. https://doi.org/10.1091/mbc.E08-08-0839
Tcherpakov M, Broday L, Delaunay A, Kadoya T, Khurana A, Erdjument-Bromage H et al. JAMP optimizes ERAD to protect cells from unfolded proteins. Molecular Biology of the Cell. 2008 Nov;19(11):5019-5028. https://doi.org/10.1091/mbc.E08-08-0839
Tcherpakov, Marianna ; Broday, Limor ; Delaunay, Agnes ; Kadoya, Takayuki ; Khurana, Ashwani ; Erdjument-Bromage, Hediye ; Tempst, Paul ; Qiu, Xiao Bo ; Demartino, George N. ; Ronai, Zéev. / JAMP optimizes ERAD to protect cells from unfolded proteins. In: Molecular Biology of the Cell. 2008 ; Vol. 19, No. 11. pp. 5019-5028.
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