RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data

Area of Science:

• Molecular Biology
• Cell Signaling
• Biochemistry

Background:

• The p90 ribosomal S6 kinase (RSK) family comprises four serine/threonine protein kinases activated by ERK1/2 and PDK1.
• RSK acts as a key signaling node due to its integration of multiple signaling pathways, implicating it in numerous pathologies.
• While many RSK substrates are known, their specific roles in disease pathogenesis remain largely uncharacterized.

Purpose of the Study:

• To identify RSK substrates common across various pathologies, including cancer, cardiovascular disease, and neurobiological disorders.
• To elucidate fundamental physiological responses mediated by RSK signaling.
• To address the paucity of literature on RSK function in inflammation, a critical aspect given ongoing clinical trials for RSK inhibitors.

Main Methods:

• Literature review and analysis of existing studies on RSK1/2 and their substrates.
• Identification of common RSK substrates across different disease contexts.
• Cross-referencing substrate roles with known pathological mechanisms.

Main Results:

• RSK1/2 signaling is implicated in a wide range of diseases, with a significant overlap in substrates related to immune response and inflammation.
• Key RSK substrates involved in cancer, cardiovascular, and neurological disorders were identified.
• The study highlights the potential of RSK inhibitors as a therapeutic strategy for diverse diseases.

Conclusions:

• RSK signaling plays a fundamental role in various pathologies, particularly those involving immune responses and inflammation.
• Identifying common RSK substrates provides insights into core physiological mechanisms underlying disease.
• Targeting RSK pathways holds promise for developing novel treatments for conditions such as metastatic breast cancer and other disorders.