RSK1 and RSK2 serine/threonine kinases regulate different transcription programs in cancer.

Autor:	Yang WS; Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, HI, United States., Caliva MJ; Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, HI, United States., Khadka VS; Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States., Tiirikainen M; Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, HI, United States., Matter ML; Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, HI, United States., Deng Y; Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States., Ramos JW; Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, HI, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2023 Jan 04; Vol. 10, pp. 1015665. Date of Electronic Publication: 2023 Jan 04 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.1015665
Abstrakt:	The 90 kDa ribosomal S6 kinases (RSKs) are serine threonine kinases comprising four isoforms. The isoforms can have overlapping functions in regulation of migration, invasion, proliferation, survival, and transcription in various cancer types. However, isoform specific differences in RSK1 versus RSK2 functions in gene regulation are not yet defined. Here, we delineate ribosomal S6 kinases isoform-specific transcriptional gene regulation by comparing transcription programs in RSK1 and RSK2 knockout cells using microarray analysis. Microarray analysis revealed significantly different mRNA expression patterns between RSK1 knockout and RSK2 knockout cell lines. Importantly some of these functions have not been previously recognized. Our analysis revealed RSK1 has specific roles in cell adhesion, cell cycle regulation and DNA replication and repair pathways, while RSK2 has specific roles in the immune response and interferon signaling pathways. We further validated that the identified gene sets significantly correlated with mRNA datasets from cancer patients. We examined the functional significance of the identified transcriptional programs using cell assays. In alignment with the microarray analysis, we found that RSK1 modulates the mRNA and protein expression of Fibronectin1, affecting cell adhesion and CDK2, affecting S-phase arrest in the cell cycle, and impairing DNA replication and repair. Under similar conditions, RSK2 showed increased ISG15 transcriptional expression, affecting the immune response pathway and cytokine expression. Collectively, our findings revealed the occurrence of RSK1 and RSK2 specific transcriptional regulation, defining separate functions of these closely related isoforms. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Yang, Caliva, Khadka, Tiirikainen, Matter, Deng and Ramos.)
Databáze:	MEDLINE
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