Cell Stress and Chaperones

, Volume 23, Issue 4, pp 527–537 | Cite as

Yeast polyubiquitin gene UBI4 deficiency leads to early induction of apoptosis and shortened replicative lifespan

  • Wei Zhao
  • Tao Zhou
  • Hua-Zhen Zheng
  • Kun-Pei Qiu
  • Hong-Jing Cui
  • Hui Yu
  • Xin-Guang LiuEmail author
Original Paper


Ubiquitin is a 76-amino acid protein that is highly conserved among higher and lower eukaryotes. The polyubiquitin gene UBI4 encodes a unique precursor protein that contains five ubiquitin repeats organized in a head-to-tail arrangement. Although the involvement of the yeast polyubiquitin gene UBI4 in the stress response was reported long ago, there are no reports regarding the underlying mechanism of this involvement. In this study, we used UBI4-deletion and UBI4-overexpressing yeast strains as models to explore the potential mechanism by which UBI4 protects yeast cells against paraquat-induced oxidative stress. Here, we show that ubi4Δ cells exhibit oxidative stress, an apoptotic phenotype, and a decreased replicative lifespan. Additionally, the reduced resistance of ubi4Δ cells to paraquat that was observed in this study was rescued by overexpression of either the catalase or the mitochondrial superoxide dismutase SOD2. We also demonstrated that only SOD2 overexpression restored the replicative lifespan of ubi4Δ cells. In contrast to the case of ubi4Δ cells, UBI4 overexpression in wild-type yeast increases the yeast’s resistance to paraquat, and this overexpression is associated with large pools of expressed ubiquitin and increased levels of ubiquitinated proteins. Collectively, these findings highlight the role of the polyubiquitin gene UBI4 in apoptosis and implicate UBI4 as a modulator of the replicative lifespan.


Yeast UBI4 Apoptosis Replicative lifespan 



We are grateful to Brian K. Kennedy (Buck Institute), Matt Kaeberlein, and Brian M. Wasko (University of Washington) for technical assistance.

Funding information

This work was supported by the China National Natural Science Foundation (31101051, 81671399), the Ordinary University Innovation Team Construction Project of Guangdong Province (2015KCXTD022), the Unique Innovative Projects in Ordinary University of Guangdong Province (2015KTSCX049), and the Guangdong Medical Research Foundation (A2016257).

Supplementary material

12192_2017_860_MOESM1_ESM.docx (119 kb)
Suppl. Fig 1 (DOCX 119 kb).
12192_2017_860_MOESM2_ESM.docx (88 kb)
Suppl. Fig 2 (DOCX 87 kb).
12192_2017_860_MOESM3_ESM.xls (28 kb)
Table S1 (XLS 27 kb).
12192_2017_860_MOESM4_ESM.xls (26 kb)
Table S2 (XLS 25 kb).


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Copyright information

© Cell Stress Society International 2017

Authors and Affiliations

  • Wei Zhao
    • 1
    • 2
  • Tao Zhou
    • 1
    • 2
  • Hua-Zhen Zheng
    • 1
    • 3
  • Kun-Pei Qiu
    • 1
    • 2
  • Hong-Jing Cui
    • 1
    • 2
  • Hui Yu
    • 1
    • 2
  • Xin-Guang Liu
    • 1
    • 2
    • 4
    Email author
  1. 1.Institute of Aging ResearchGuangdong Medical UniversityDongguanChina
  2. 2.Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsDongguanChina
  3. 3.Department of Clinical LaboratoryThe First People’s Hospital of FoshanFoshanChina
  4. 4.Institute of Biochemistry and Molecular BiologyGuangdong Medical UniversityDongguanChina

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