RPS6KB1

Fig1. Schematic of mTORC1 signalling in live cells showing possible S6K1 recruitment onto mTORC1. (Abdullah R Ahmed, 2019)

What is RPS6KB1 protein?

RPS6KB1 (ribosomal protein S6 kinase B1) gene is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q23. This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The RPS6KB1 protein is consisted of 525 amino acids and its molecular mass is approximately 59.1 kDa.

What is the function of RPS6KB1 protein?

Activated RPS6KB1 promotes protein synthesis by phosphorylating multiple substrates, including ribosomal protein S6 (rpS6) and other factors involved in mRNA translation, which affects cell growth and size. RPS6KB1 plays an important role in cell growth and metabolism, especially in the presence of adequate nutrition. It responds to cellular nutritional status and growth factor signals by regulating protein synthesis and lipid metabolism. RPS6KB1 is also involved in cellular responses to stress, such as oxidative stress and DNA damage. It may regulate cell survival and death by influencing the process of cell cycle and apoptosis. RPS6KB1 is involved in cell cycle regulation by phosphorylating cell cycle-related proteins, such as cycle-dependent kinase inhibitory protein p27^Kip1, which affects cell proliferation and differentiation.

RPS6KB1 Related Signaling Pathway

RPS6KB1, also known as S6K1, is a serine/threonine kinase that is primarily involved in the mTOR signaling pathway. mTOR (Mammalian Target Protein) is a key protein kinase that integrates a variety of intracellular and extracellular signals, including growth factors, nutrient levels, energy status, and environmental stress, to regulate cell growth, proliferation, metabolism, and survival.

The role of S6K1 in the mTOR signaling pathway is primarily as a direct substrate for mTOR complex 1 (mTORC1). When mTORC1 is activated, it phosphorylates S6K1, which boosts its kinase activity. Activated S6K1 further phosphorylates its downstream substrates, including ribosomal protein S6 (rpS6), which is its best known substrate, a process that promotes protein synthesis and cell growth.

RPS6KB1 Related Diseases

RPS6KB1 is an important serine/threonine kinase, which is closely related to the occurrence and development of many diseases. Due to its role in protein synthesis, cell growth, and metabolic regulation, abnormal activity of RPS6KB1 has been associated with a variety of metabolic diseases such as type 2 diabetes and obesity. In addition, RPS6KB1 also plays a key role in tumor biology, and its overactivation has been linked to the progression of multiple cancers such as breast cancer and lung cancer, making it a potential target for cancer therapy. RPS6KB1 is also associated with several neurodegenerative diseases, such as Parkinson's disease and multiple sclerosis, and may be involved in the pathogenesis of these diseases by affecting cell signaling and cell survival pathways. In addition, RPS6KB1 is also associated with the pathological processes of rare diseases such as Tuberous Sclerosis and Lymphangioleiomyomatosis.

Bioapplications of RPS6KB1

As a marker of mTORC1 activity, S6K1 is often used to evaluate the effects of mTOR inhibitors and as a target or biomarker during drug screening and development. S6K1 is overactivated in many types of cancer, promoting the proliferation and survival of tumor cells. Therefore, the development of small molecule drugs that inhibit S6K1 activity could be used as a potential strategy for anti-cancer therapy, either alone or in combination with other treatments such as chemotherapy, radiation, or immunotherapy.