RHEB Human

RHEB is a 21 kDa protein composed of 184 amino acids. The first 169 amino acids form the GTPase domain, while the remaining amino acids constitute a hypervariable region ending at the C-terminus in a CAAX motif (C – cysteine, A – aliphatic amino acid, X – C-terminus amino acid) . This structure allows RHEB to bind and hydrolyze GTP, a critical function for its role in signal transduction.

RHEB is a key regulator of the mTOR pathway, which is essential for cell growth, proliferation, and survival. The mTOR pathway integrates signals from nutrients, growth factors, and cellular energy status to control protein synthesis and other anabolic processes. RHEB activates mTORC1 (mechanistic target of rapamycin complex 1) by directly binding to it, leading to the phosphorylation of downstream targets that promote cell growth and proliferation .

Overexpression of RHEB has been observed in multiple human carcinomas, making it a potential target for cancer therapy . The dysregulation of the mTOR pathway, often due to aberrant RHEB activity, can lead to uncontrolled cell growth and tumor development. Researchers are exploring ways to inhibit RHEB to control the mTOR pathway as a treatment for various cancers, including tuberous sclerosis .

RHEB also plays a significant role in neuronal activity. It is involved in the regulation of synaptic plasticity, which is crucial for learning and memory. The protein’s function in neurons is linked to its ability to modulate the mTOR pathway, affecting processes such as protein synthesis and autophagy .

Given its central role in both cancer and neuronal dynamics, RHEB is a promising target for therapeutic interventions. Inhibitors of RHEB are being investigated for their potential to treat cancers characterized by mTOR pathway dysregulation. Additionally, understanding RHEB’s role in neurons could lead to new treatments for neurological disorders .