Back to Search
Start Over
The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2019
- Publisher :
- Rockefeller University Press, 2019.
-
Abstract
- How resident inner nuclear membrane (INM) proteins are turned over is unclear. Koch et al. identify an APC/C-dependent mechanism controlling the degradation of Mps3, a conserved integral protein of the INM.<br />The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. Turnover of ER proteins has been well characterized by the ER-associated protein degradation (ERAD) pathway, but very little is known about turnover of resident INM proteins. Here we show that the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, regulates the degradation of Mps3, a conserved integral protein of the INM. Turnover of Mps3 requires the ubiquitin-conjugating enzyme Ubc7, but was independent of the known ERAD ubiquitin ligases Doa10 and Hrd1 as well as the recently discovered Asi1–Asi3 complex. Using a genetic approach, we have found that Cdh1, a coactivator of APC/C, modulates Mps3 stability. APC/C controls Mps3 degradation through Mps3’s N terminus, which resides in the nucleoplasm and possesses two putative APC/C-dependent destruction motifs. Accumulation of Mps3 at the INM impairs nuclear morphological changes and cell division. Our findings therefore reveal an unexpected mechanism of APC/C-mediated protein degradation at the INM that coordinates nuclear morphogenesis and cell cycle progression.
- Subjects :
- Saccharomyces cerevisiae Proteins
Nuclear Envelope
Ubiquitin-Protein Ligases
Saccharomyces cerevisiae
Endoplasmic-reticulum-associated protein degradation
Protein degradation
Article
Anaphase-Promoting Complex-Cyclosome
Cdh1 Proteins
03 medical and health sciences
0302 clinical medicine
Inner membrane
Integral membrane protein
Research Articles
030304 developmental biology
0303 health sciences
Nucleoplasm
biology
Protein Stability
Endoplasmic reticulum
Membrane Proteins
Nuclear Proteins
Endoplasmic Reticulum-Associated Degradation
Cell Biology
Cell biology
Ubiquitin ligase
Proteolysis
biology.protein
Anaphase-promoting complex
Cell Division
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 218
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....fc29d1afeee0dfb49bdc2e4afb1e4cf6