Ribosomal protein S6 kinase beta-1 (RPS6KB1) (RPS6KB1)

Ribosomal protein S6 kinase beta-1 (RPS6KB1), commonly known as p70S6K, is a serine/threonine-protein kinase that functions as a principal downstream effector of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway (UniProt P23443). It plays a fundamental role in regulating protein synthesis, cell growth, and cell cycle progression by phosphorylating the S6 subunit of the 40S ribosome and other substrates involved in mRNA translation (PubMed: 12150925). RPS6KB1 is frequently overexpressed or amplified in various malignancies, including breast and lung cancers, where it contributes to uncontrolled cell proliferation and therapeutic resistance (NCBI Gene: 6198). Beyond oncology, it is implicated in metabolic diseases such as type 2 diabetes due to its role in mediating insulin resistance through a negative feedback loop on insulin receptor substrate 1 (IRS-1) (PubMed: 15057245). While most clinical targeting occurs indirectly via mTOR inhibitors like Everolimus, selective RPS6KB1 inhibitors such as PF-4708671 are being investigated to provide more targeted therapy with fewer systemic side effects (PubChem CID 44147665).

Other names

p70S6Kp70-S6KS6K1STK14APS6KRibosomal protein S6 kinase I

Inhibition of the serine/threonine kinase activity of RPS6KB1, which prevents the phosphorylation of the 40S ribosomal protein S6 and other substrates, thereby inhibiting protein synthesis and cell cycle progression (PubMed: 12150925).