Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Ubiquitin-recognition protein Ufd1 couples the endoplasmic reticulum (ER) stress response to cell cycle control.

http://www.ncbi.nlm.nih.gov/pubmed/21571647

The ubiquitin-recognition protein Ufd1 facilitates clearance of misfolded proteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. Here we report that prolonged ER stress represses Ufd1 expression to trigger cell cycle delay, which contributes to ERAD. Remarkably, down-regulation of Ufd1 enhances ubiquitination and destabilization of Skp2 mediated by the anaphase-promoting complex or cyclosome bound to Cdh1 (APC/C(Cdh1)), resulting in accumulation of the cyclin-dependent kinase inhibitor p27 and a concomitant cell cycle delay during the G1 phase that enables more efficient clearance of misfolded proteins. Mechanistically, nuclear Ufd1 recruits the deubiquitinating enzyme USP13 to counteract APC/C(Cdh1)-mediated ubiquitination of Skp2. Our data identify a coordinated cell cycle response to prolonged ER stress through regulation of the Cdh1-Skp2-p27 axis by Ufd1 and USP13.

Pubmed ID: 21571647 RIS Download

Mesh terms: Binding Sites | Cell Cycle | Cell Separation | Down-Regulation | Endoplasmic Reticulum | Flow Cytometry | Gene Expression Regulation, Fungal | HeLa Cells | Humans | Mutation | Protein Structure, Tertiary | Proteins | S-Phase Kinase-Associated Proteins | Saccharomyces cerevisiae | Tunicamycin

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: 5T32CA077109
  • Agency: NCI NIH HHS, Id: CA097105
  • Agency: NCI NIH HHS, Id: CA78419
  • Agency: NCI NIH HHS, Id: R01 CA138143
  • Agency: NCI NIH HHS, Id: T32 CA077109

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.