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Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates.

Publication ,  Journal Article
Nowis, D; McConnell, E; Wójcik, C
Published in: Experimental cell research
September 2006

p97/VCP associated with Ufd1-Npl4 is considered a key player in ER-associated degradation (ERAD). RNA interference (RNAi) of one component of the Ufd1-Npl4 heterodimer destabilizes the VCP-Ufd1-Npl4 complex inducing proteasome-dependent degradation of the other component and releasing free VCP. In contrast to RNAi of VCP, RNAi of Ufd1 or Npl4 depleting approximately 90% of the VCP-Ufd1-Npl4 complexes does not induce unfolded protein response, indicating that the Ufd1-Npl4 dimer is not involved in the regulation of ER function by VCP. RNAi of Ufd1 or Npl4 is associated with a 2-fold increase in the levels of polyubiquitinated proteins, which form dispersed aggregates often associated with calnexin-positive structures. However, contrary to the effects of proteasome inhibition, RNAi of Ufd1 or Npl4 does not induce an accumulation of alpha-TCR and delta-CD3, two ERAD substrates overexpressed in HeLa cells. Instead, a 60-70% decrease in their levels is observed. The decrease in alpha-TCR levels is associated with a 50% decrease of its half-life. Upregulation of the putative channel forming protein, derlin-1, may contribute to the increased degradation of ERAD substrates. To explain our findings, we propose a model, where association of emerging ERAD substrates with VCP-Ufd1-Npl4 is not required for their degradation but has a regulatory role.

Duke Scholars

Published In

Experimental cell research

DOI

EISSN

1090-2422

ISSN

0014-4827

Publication Date

September 2006

Volume

312

Issue

15

Start / End Page

2921 / 2932

Related Subject Headings

  • Valosin Containing Protein
  • Up-Regulation
  • Ubiquitins
  • Substrate Specificity
  • Receptors, Antigen, T-Cell, alpha-beta
  • RNA Interference
  • Proteins
  • Nuclear Proteins
  • Microscopy, Fluorescence
  • Membrane Proteins
 

Citation

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MLA
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Nowis, D., McConnell, E., & Wójcik, C. (2006). Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates. Experimental Cell Research, 312(15), 2921–2932. https://doi.org/10.1016/j.yexcr.2006.05.013
Nowis, Dominika, Elizabeth McConnell, and Cezary Wójcik. “Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates.Experimental Cell Research 312, no. 15 (September 2006): 2921–32. https://doi.org/10.1016/j.yexcr.2006.05.013.
Nowis D, McConnell E, Wójcik C. Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates. Experimental cell research. 2006 Sep;312(15):2921–32.
Nowis, Dominika, et al. “Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates.Experimental Cell Research, vol. 312, no. 15, Sept. 2006, pp. 2921–32. Epmc, doi:10.1016/j.yexcr.2006.05.013.
Nowis D, McConnell E, Wójcik C. Destabilization of the VCP-Ufd1-Npl4 complex is associated with decreased levels of ERAD substrates. Experimental cell research. 2006 Sep;312(15):2921–2932.
Journal cover image

Published In

Experimental cell research

DOI

EISSN

1090-2422

ISSN

0014-4827

Publication Date

September 2006

Volume

312

Issue

15

Start / End Page

2921 / 2932

Related Subject Headings

  • Valosin Containing Protein
  • Up-Regulation
  • Ubiquitins
  • Substrate Specificity
  • Receptors, Antigen, T-Cell, alpha-beta
  • RNA Interference
  • Proteins
  • Nuclear Proteins
  • Microscopy, Fluorescence
  • Membrane Proteins