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PSMA2 knockdown impacts expression of proteins involved in immune and cellular stress responses in human lung cells
Mahamud-Ur Rashid1, Shahrokh Lorzadeh2, Ang Gao3
1University 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.
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.
Insights
Knocking down proteasome subunit alpha type-2 (PSMA2) significantly altered 52 cellular proteins, impacting immune response, cell signaling, and cancer pathways in lung epithelial cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Proteomics
Background:
- Proteasome subunit alpha type-2 (PSMA2) is crucial for the 20S proteasome, essential for cellular protein quality control.
- Dysregulated PSMA2 expression is linked to human diseases and viral infections.
- The impact of PSMA2 knockdown on the cellular proteome remains unstudied.
Purpose of the Study:
- To investigate the global proteomic changes following PSMA2 knockdown in human lung epithelial cells.
- To identify cellular functions and signaling pathways affected by PSMA2 dysregulation.
Main Methods:
- Utilized SOMAScan, an aptamer-based multiplexed assay, to quantify over 1300 human proteins.
- Performed PSMA2 knockdown in A549 human lung epithelial cells.
Main Results:
- PSMA2 knockdown led to significant dysregulation of 52 cellular proteins.
- Affected biological functions included cellular movement, development, cell death, survival, and cancer.
- Immune system and signal transduction pathways were notably impacted, including cytokine signaling, autophagy, and unfolded protein response.
Conclusions:
- This study elucidates the critical role of PSMA2 in diverse cellular functions and signaling pathways.
- Findings provide insights into the involvement of PSMA2 in human diseases.
