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Role of PSMD5 Protein–Protein Interactions in Proteasome Assembly and Cancer
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788244
*Corresponding author: (e-mail: apanda@actrec.gov.in).
Abstract
Background: 26S proteasome assembly chaperone PSMD5, upon overexpression, inhibits proteasome assembly and activity. Many cancer cells show decreased PSMD5 expression, possibly as an adaptation to proteotoxic stress. This study investigates the molecular link between proteotoxic stress and PSMD5 levels as well as discovers and characterizes PSMD5 interactomes and their associated functions.
Materials and Methods: Breast cancer cell lines, including MCF7, MDA-MB-231, T47D, and ZR75.1, were screened for PSMD5 levels. Proteasome assembly and activity were checked by native-PAGE and fluorescence-based assays, respectively. PSMD5 was transiently overexpressed in MDA-MB-231 using the PSMD5-pcDNA3.1 vector. Affinity purification coupled mass-spectrometry (AP-MS) is being used to investigate PSMD5′s novel interactions.
Results: Comparative analysis of several cancer cell lines showed that levels of PSMD5 are very low in MDA-MB-231, while the corresponding proteasome assembly and activity are higher than in other cell lines such as T47D, MCF7, and ZR75.1. This inverse correlation was further confirmed upon overexpression of PSMD5 in the MDA-MB-231 cell line, which decreased the total proteasome level and activity.
Conclusions: Recent studies and our preliminary results from breast cancer cells suggest that PSMD5 quantum is crucial for 26S proteasome activity. Strategies to inhibit PSMD5 levels, function, and interaction could help regulate homeostasis and overcome proteotoxicity. AP-MS could help identify other interacting partners of PSMD5 and their mechanisms for proteostasis regulation.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: apanda@actrec.gov.in).
Abstract
Background: 26S proteasome assembly chaperone PSMD5, upon overexpression, inhibits proteasome assembly and activity. Many cancer cells show decreased PSMD5 expression, possibly as an adaptation to proteotoxic stress. This study investigates the molecular link between proteotoxic stress and PSMD5 levels as well as discovers and characterizes PSMD5 interactomes and their associated functions.
Materials and Methods: Breast cancer cell lines, including MCF7, MDA-MB-231, T47D, and ZR75.1, were screened for PSMD5 levels. Proteasome assembly and activity were checked by native-PAGE and fluorescence-based assays, respectively. PSMD5 was transiently overexpressed in MDA-MB-231 using the PSMD5-pcDNA3.1 vector. Affinity purification coupled mass-spectrometry (AP-MS) is being used to investigate PSMD5′s novel interactions.
Results: Comparative analysis of several cancer cell lines showed that levels of PSMD5 are very low in MDA-MB-231, while the corresponding proteasome assembly and activity are higher than in other cell lines such as T47D, MCF7, and ZR75.1. This inverse correlation was further confirmed upon overexpression of PSMD5 in the MDA-MB-231 cell line, which decreased the total proteasome level and activity.
Conclusions: Recent studies and our preliminary results from breast cancer cells suggest that PSMD5 quantum is crucial for 26S proteasome activity. Strategies to inhibit PSMD5 levels, function, and interaction could help regulate homeostasis and overcome proteotoxicity. AP-MS could help identify other interacting partners of PSMD5 and their mechanisms for proteostasis regulation.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India