Highlight Issue for Fred Wittinghofer on GTP/GDP binding proteins:
New Review Article published in Biological Chemistry describes
„Mechanistic insights on spatiotemporal control of Ras-signaling“
Proteins of the Ras-family are guanine nucleotide binding proteins (GNBPs) involved in a variety of fundamental cellular processes, including cell proliferation, cell di erentiation, cytoskeleton dynamics, vesicular processes and intracellular transport. A dysregulation of Ras-signaling has been found to be causative for the development of diseases, such as diverse cancer types, RASopathies, neurodegenerative diseases and ciliopathies. Ras-proteins cycle between a GTP-bound on-state and a GDP-bound o -state. Ras-proteins show low intrinsic rates for nucleotide exchange and nucleotide hydrolysis. They need guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) to accelerate both functions in order to act as true molecular switches in the physiological context. Ras-proteins and their regulators/e ectors are targets of posttranslational modi cations (PTMs) such as phosphorylation, ac(et)ylation, lipidation and ubiquitination. These PTMs regulate their activity, subcellular localization and turnover. In a biological perspective, PTMs are essential components for cellular signaling cascades and for molecular pattern formation. Bacterial pathogens use PTMs of Ras-proteins to allow e cient infection processes. Besides, modi cations of Ras-proteins were shown to be of therapeutic potential in oncogenic variants such as Ras G12C. In this review, we summarize current knowledge on Ras-signaling, while emphasizing PTMs as dynamic signaling hubs for its precise spatiotemporal control.
You can access the publication following this link.
Charrier C, Mrachacz S, Schulze S, Lammers M. (2026) Mechanistic insights on spatiotemporal control of Ras-signaling. Biol Chem. 407(1-3):25-66. doi: 10.1515/hsz-2025-0243. PMID: 42105364.