Involvement of Sec71 and Ubp2 in tunicamycin-induced ER stress response in the fission yeast.

Yemenici M., Kartal Sural B., Karaer Uzuner S., Palabıyık B.

Molecular biology reports, cilt.49, sa.6, ss.4719-4726, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 49 Sayı: 6
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s11033-022-07321-4
  • Dergi Adı: Molecular biology reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.4719-4726
  • Anahtar Kelimeler: ER stress, Apoptosis, Tunicamycin, Vesicular transport, Deubiquitination, ENDOPLASMIC-RETICULUM STRESS, UNFOLDED PROTEIN RESPONSE, UBIQUITIN-PROTEASOME SYSTEM, CELL-DEATH, OXIDATIVE STRESS, ARF GTPASES, TRAFFICKING, TRANSPORT, PATHWAY, GOLGI
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background Accumulation of unfolded or misfolded proteins in the cellular environment result in ER stress and activates the unfolded protein response (UPR). The UPR alleviates ER stress and restores homeostasis, but it triggers cell death under prolonged stress. Here, we aimed to investigate the involvement of Sec71, an Arf-GEF involved in vesicular transport, in the tunicamycin-induced ER stress response. Since deubiquitinases and ER stress are known to be closely linked, we investigated this response by evaluating the potential role of Ubp2, a deubiquitinase, in the ER stress response in fission yeast. Methods and results Tunicamycin-induced ER stress responses were assessed by analyzing cell viability, apoptosis, intracellular oxidation levels, and proteasomal activities in sec71 and ubp2-deficient cells. The cell viability of Delta sec71 and Delta ubp2 decreased after exposure to 0.5 mu g/mL tunicamycin. Deleting either ubp2 or sec71 genes significantly decreased proteasomal activity and sensitized cells to ER stress, resulting in increased apoptosis compared with wild-type cells after tunicamycin treatment. DCFDA (2,7-dichlorodihydrofluorescein diacetate) reduction increased in correlation with apoptosis observed in the mutant cells, indicating higher levels of reactive oxygen species. Conclusions The results highlight the involvement of S. pombe Ubp2 in the known role of the ubiquitin-proteasome system in the ER stress response. We hypothesise that Sec71 is associated with ER homeostasis, and our findings on Sec71 provide new insight into the regulation of cell death mechanisms arising from the ER stress.