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PSMA2 knockdown impacts expression of proteins involved in immune and cellular stress responses in human lung cells
Institution:1. University of Manitoba, Department of Medical Microbiology & Infectious Diseases, Room 543 Basic Medical Sciences Building, 745 Bannatyne Ave., Winnipeg, MB R3E 0J9, Canada;2. Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada;3. Department of Human Anatomy and Cell Science, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0V9, Canada;4. Research Institutes of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, MB R3E 0V9, Canada;5. Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada;6. Children''s Hospital Research Institute of Manitoba, Room 513, 715 McDermot Ave., Winnipeg, MB R3E 3P4, Canada
Abstract: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.
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