P70-S6 Kinase 1

P70-S6 Kinase 1 (p70S6K1) is a protein kinase that is encoded by the RPS6KB1 gene in humans. It is a member of the serine/threonine kinase family and plays a crucial role in the control of cell growth and proliferation by modulating the synthesis of proteins. p70S6K1 acts downstream of the PI3K-AKT/mTOR pathway, which is activated by various growth factors, cytokines, and hormones.

Function

p70S6K1 is primarily known for its role in the regulation of protein synthesis. It phosphorylates the S6 ribosomal protein, leading to an increase in the translation of mRNAs with oligopyrimidine tracts at their transcriptional start sites. These mRNAs often encode components of the protein synthesis machinery, thus p70S6K1 activity enhances the capacity of the cell to synthesize proteins. The kinase is also involved in the regulation of cell size, glucose homeostasis, and lipid metabolism. Its activity is regulated by nutritional and hormonal signals, highlighting its role in the adaptation of cell growth in response to environmental cues.

Activation

The activation of p70S6K1 is complex and involves multiple steps, including phosphorylation by mTORC1 (mechanistic target of rapamycin complex 1) in response to growth factors, energy status, oxygen, and amino acids availability. The TSC1-TSC2 complex acts as a negative regulator of mTORC1, and thus of p70S6K1, linking the kinase's activity to cellular energy status and stress responses.

Clinical Significance

Alterations in the PI3K-AKT-mTOR-p70S6K pathway are implicated in various human diseases, including cancers, Obesity, diabetes, and Neurodegenerative diseases. Due to its central role in cell growth and metabolism, p70S6K1 is considered a potential therapeutic target. Inhibitors of p70S6K1 are being explored for the treatment of cancer and metabolic disorders.

Inhibitors

Several small molecule inhibitors targeting p70S6K1 have been developed, with the aim of suppressing aberrant cell growth and proliferation in cancer. These inhibitors are in various stages of preclinical and clinical development. By inhibiting p70S6K1, these compounds can reduce protein synthesis in cancer cells, leading to cell cycle arrest and apoptosis.

See Also

• mTOR inhibitors
• Protein kinase B
• Ribosomal protein S6