PMID- 36481484 OWN - NLM STAT- MEDLINE DCOM- 20221221 LR - 20230217 IS - 1879-260X (Electronic) IS - 0925-4439 (Linking) VI - 1869 IP - 2 DP - 2023 Feb TI - PSMA2 knockdown impacts expression of proteins involved in immune and cellular stress responses in human lung cells. PG - 166617 LID - S0925-4439(22)00288-5 [pii] LID - 10.1016/j.bbadis.2022.166617 [doi] AB - Proteasome subunit alpha type-2 (PSMA2) is a critical component of the 20S proteasome, which is the core particle of the 26S proteasome complex and is involved in cellular protein quality control by recognizing and recycling defective proteins. PSMA2 expression dysregulation has been detected in different human diseases and viral infections. No study yet has reported PSMA2 knockdown (KD) effects on the cellular proteome. METHODS: We used SOMAScan, an aptamer-based multiplexed technique, to measure >1300 human proteins to determine the impact of PSMA2 KD on A549 human lung epithelial cells. RESULTS: PSMA2 KD resulted in significant dysregulation of 52 cellular proteins involved in different bio-functions, including cellular movement and development, cell death and survival, and cancer. The immune system and signal transduction were the most affected cellular functions. PSMA2 KD caused dysregulation of several signaling pathways involved in immune response, cytokine signaling, organismal growth and development, cellular stress and injury (including autophagy and unfolded protein response), and cancer responses. CONCLUSIONS: In summary, this study helps us better understand the importance of PSMA2 in different cellular functions, signaling pathways, and human diseases. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Rashid, Mahamud-Ur AU - Rashid MU AD - University of Manitoba, Department of Medical Microbiology & Infectious Diseases, Room 543 Basic Medical Sciences Building, 745 Bannatyne Ave., Winnipeg, MB R3E 0J9, Canada; Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada. FAU - Lorzadeh, Shahrokh AU - Lorzadeh S AD - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0V9, Canada. FAU - Gao, Ang AU - Gao A AD - Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada. FAU - Ghavami, Saeid AU - Ghavami S AD - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0V9, Canada; Research Institutes of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, MB R3E 0V9, Canada; Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada. FAU - Coombs, Kevin M AU - Coombs KM AD - University of Manitoba, Department of Medical Microbiology & Infectious Diseases, Room 543 Basic Medical Sciences Building, 745 Bannatyne Ave., Winnipeg, MB R3E 0J9, Canada; Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada; Children's Hospital Research Institute of Manitoba, Room 513, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada. Electronic address: kevin.coombs@umanitoba.ca. LA - eng GR - MOP-106713/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221205 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 RN - 0 (Proteome) SB - IM MH - Humans MH - *Unfolded Protein Response MH - *Proteome/metabolism MH - Signal Transduction MH - Lung/metabolism OTO - NOTNLM OT - Autophagy, endoplasmic reticulum stress OT - Immune system OT - PSMA2 OT - Proteasome OT - Signal transduction COIS- Declaration of competing interest Kevin M. Coombs reports financial support was provided by Canadian Institutes of Health Research. Mahamud ur-Rashid reports financial support was provided by Research Manitoba. Saeid Ghavami reports financial support was provided by Research Manitoba. EDAT- 2022/12/09 06:00 MHDA- 2022/12/22 06:00 CRDT- 2022/12/08 23:35 PHST- 2022/07/12 00:00 [received] PHST- 2022/11/21 00:00 [revised] PHST- 2022/11/28 00:00 [accepted] PHST- 2022/12/09 06:00 [pubmed] PHST- 2022/12/22 06:00 [medline] PHST- 2022/12/08 23:35 [entrez] AID - S0925-4439(22)00288-5 [pii] AID - 10.1016/j.bbadis.2022.166617 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2023 Feb;1869(2):166617. doi: 10.1016/j.bbadis.2022.166617. Epub 2022 Dec 5.