A Rational Design of α-Helix-Shaped Peptides Employing the Hydrogen-Bond Surrogate Approach: A Modulation Strategy for Ras-RasGRF1 Interaction in Neuropsychiatric Disorders by Maria Rita Gulotta, Riccardo Brambilla, Ugo Perricone, Andrea Brancale

“…Previously, we showed that a cell penetrating peptide, RB3, was able to inhibit downstream signalling by preventing RasGRF1 (Ras guanine nucleotide-releasing factor 1), a neuronal specific GDP/GTP exchange factor, to bind Ras proteins, both in brain slices and in vivo, with an IC₅₀ value in the micromolar range. …”
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Characterisation of a cyclic peptide that binds to the RAS binding domain of phosphoinositide 3-kinase p110α by Mohamed Ismail, Stephen R. Martin, Roger George, Francesca Houghton, Geoff Kelly, Raphaël A. G. Chaleil, Panayiotis Anastasiou, Xinyue Wang, Nicola O’Reilly, Stefania Federico, Dhira Joshi, Hemavathi Nagaraj, Rachel Cooley, Ning Sze Hui, Miriam Molina-Arcas, David C. Hancock, Ali Tavassoli, Julian Downward

“…Abstract P110α is a member of the phosphoinositide 3-kinase (PI3K) enzyme family that functions downstream of RAS. RAS proteins contribute to the activation of p110α by interacting directly with its RAS binding domain (RBD), resulting in the promotion of many cellular functions such as cell growth, proliferation and survival. …”
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Targeting KRAS in Solid Tumors: Current Challenges and Future Opportunities of Novel KRAS Inhibitors by Alice Indini, Erika Rijavec, Michele Ghidini, Alessio Cortellini, Francesco Grossi

“…Historically, KRAS has been acknowledged as “undruggable”, largely because the RAS proteins do not appear to present suitable pockets to which small inhibitory molecules can bind. …”
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A Small Molecule Promoting Neural Differentiation Suppresses Cancer Stem Cells in Colorectal Cancer by Jung Kyu Choi, Ihn-Sil Kwak, Sae-Bom Yoon, Heeyeong Cho, Byoung-San Moon

“…We previously showed that CPD0857 inactivates Wnt/β-catenin signaling by promoting the ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing the apoptosis of CRC lines. …”
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Mechanistic insights on anticancer drugs with specific biological targets and signalling pathways by Mohsina Patwekar, Faheem Patwekar, Anuradha Medikeri, Shaikh Daniyal, Mohammad A. Kamal, Gulzar Ahmed Rather, Rohit Sharma

“…As a result of mutations or altered signalling, rat sarcoma (RAS) proteins regulate signalling, which is essential for both healthy growth and the development of cancer. …”
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Autophagy Stimulus-Dependent Role of the Small GTPase Ras2 in Peroxisome Degradation by Fahd Boutouja, Harald W. Platta

“…Yeast Ras2 is homologous to the mammalian Ras proteins, whose mutant forms are responsible for 33% of human cancers. …”
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RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia by Jian-Gang Ren, Bowen Xing, Kaosheng Lv, Rachel A. O’Keefe, Mengfang Wu, Ruoxing Wang, Kaylyn M. Bauer, Arevik Ghazaryan, George M. Burslem, Jing Zhang, Ryan M. O’Connell, Vinodh Pillai, Elizabeth O. Hexner, Mark R. Philips, Wei Tong

“…RAS mutations are among the most prevalent oncogenic drivers in cancers. RAS proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that impact their trafficking. …”
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Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function by Hocker, Harrison J., Cho, Kwang Jin, Chen, Chung Ying K., Rambahal, Nandini, Sagineedu, Sreenivasa Rao, Shaari, Khozirah, Stanslas, Johnson, Hancock, John F., Gorfe, Alemayehu A.

“…Aberrant signaling by oncogenic mutant rat sarcoma (Ras)proteins occurs in ∼15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. …”

Pharmacological modulation of oncogenic Ras by natural products and their derivatives: renewed hope in the discovery of novel anti-Ras drugs by Quah, Shun Ying, Tan, Michelle Siying, Teh, Yuan Han, Stanslas, Johnson

“…The anti-Ras strategy of these compounds can be categorized into four main types: inhibition of Ras–effector interaction, interference of Ras membrane association, prevention of Ras–guanosine triphosphate (GTP) formation, and downregulation of Ras proteins. Another promising strategy that must be validated experimentally is enhancement of the intrinsic Ras–guanosine triphosphatase (GTPase) activity by small chemical entities. …”
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Liprin‐α1 contributes to oncogenic MAPK signaling by counteracting ERK activity by Henna Pehkonen, Artemis Filippou, Juho Väänänen, Iida Lindfors, Mira Vänttinen, Philipp Ianevski, Anne Mäkelä, Pauliina Munne, Juha Klefström, Sanna Toppila‐Salmi, Reidar Grénman, Jaana Hagström, Antti A. Mäkitie, Piia‐Riitta Karhemo, Outi Monni

“…Furthermore, liprin‐α1 depletion led to more pronounced redistribution of RAS proteins to the cell membrane. Our data suggest that liprin‐α1 is an important contributor to oncogenic RAS/MAPK signaling, and the status of liprin‐α1 may assist in predicting drug responses in cancer cells in a context‐dependent manner.…”
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Detection of Ras nanoclustering-dependent homo-FRET using fluorescence anisotropy measurements by Ganesh babu Manoharan, Camilo Guzmán, Arafath Kaja Najumudeen, Daniel Abankwa

“…Nanoclusters contain only a few Ras proteins and are necessary for the recruitment of downstream effectors, such as Raf. …”
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Novel Insights into the Role of Kras in Myeloid Differentiation: Engaging with Wnt/β-Catenin Signaling by Noriko Yokoyama, Hitoshi Nakayama, Kazuhisa Iwabuchi

“…This review focuses on the differentiation of HL-60 cells. Although the Ras proteins, a group of small GTP-binding proteins, are ubiquitously expressed and highly homologous, each has specific molecular functions. …”
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Molecular Origin and Functional Consequences of Digital Signaling and Hysteresis During Ras Activation in Lymphocytes by Das, Jayajit, Zikherman, Julie, Yang, Ming, Govern, Christopher C., Ho, Mary, Weiss, Arthur, Roose, Jeroen, Chakraborty, Arup K

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Protein-based Degrader Strategies against Oncogenic RAS by Cheah, Keith M.

“…Targeted therapies have emerged as a promising cancer treatment strategy by inhibiting proteins specific to cancer cells while preserving healthy cells. RAS proteins play a crucial role in cancer development and are associated with increased tumor growth and invasion. …”
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Novel Therapeutic Approaches for KRAS-Mutated Lung Cancer Involving LZTR1 Genetic Alteration by Raj N. Sewduth, Tonci Ivanisevic, Peihua Zhao, Anna A. Sablina

“…LZTR1 is an adaptor of CUL3 E3 ligase that controls the localization and expression levels of RAS proteins by regulating their ubiquitination. Recent studies demonstrated that the loss of <i>LZTR1</i> leads to resistance to the tyrosine kinase inhibitor and the multi-kinase inhibitor, suggesting that <i>LZTR1</i> loss might be associated with the drug resistance of KRAS-mutated lung tumors. …”
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C3G Is Upregulated in Hepatocarcinoma, Contributing to Tumor Growth and Progression and to HGF/MET Pathway Activation by Celia Sequera, Paloma Bragado, Sara Manzano, Maria Arechederra, Sylvie Richelme, Alvaro Gutiérrez-Uzquiza, Aránzazu Sánchez, Flavio Maina, Carmen Guerrero, Almudena Porras

“…C3G, a guanine nucleotide exchange factor for Rap and other Ras proteins, plays a dual role in cancer acting as either a tumor suppressor or promoter depending on tumor type and stage. …”
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Regulation of cell signalling by iRhoms by Sieber, B

“…Oncogenic KRas and HRas stimulate TACE activity, which demonstrates the conserved role of Ras proteins in stimulating the release of EGFR ligands by TACE. …”

Pathogen-specific structural features of Candida albicans Ras1 activation complex: uncovering new antifungal drug targets by José A. Manso, Arturo Carabias, Zsuzsa Sárkány, José M. de Pereda, Pedro José Barbosa Pereira, Sandra Macedo-Ribeiro

“…An important function in hyphal growth has also been proposed for the long hypervariable region downstream the G-domain, whose unusual content of polyglutamine stretches and Q/N repeats make CaRas1 unique within Ras proteins. Despite its biological importance, both the structure of CaRas1 and the molecular basis of its activation by CaCdc25 remain unexplored. …”
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RGD-p21Ras-scFv expressed prokaryotically on a pilot scale inhibits ras-driven colorectal cancer growth by blocking p21Ras-GTP by Peng Lin, Jing Qian, Cheng-Cheng Huang, Wen-Mang Xu, Yuan-Yuan Wang, Zi-Ran Gao, Shi-Qi Zheng, Peng Wang, Da-Qi Jia, Qiang Feng, Ju-Lun Yang

“…ELISA was adopted to test the immunoreactivity of RGD-p21Ras-scFv against p21Ras proteins, and the IC50 of RGD-p21Ras-scFv was analyzed by CCK-8. …”
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Functional characterization of Rasd1 : a novel interaction between Rasd1 and Ear2 (NR2F6) is involved in the regulation of renin transcription by Tan, Jen Jen

“…The characteristic GTP binding and hydrolysis properties of Ras proteins render Rasd1 extremely important in numerous signaling pathways and physiological processes. …”
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