The family of Rho GTPases are involved in the dynamic control of cytoskeleton reorganization and other fundamental cellular functions, including growth, motility, and survival. Rac1, one of the best characterized Rho GTPases, is an established effector of receptors and an important node in signaling networks crucial for tumorigenesis and metastasis. Rac1 hyperactivation is common in human cancer and could be the consequence of overexpression, abnormal upstream inputs, deregulated degradation, and/or anomalous intracellular localization. More recently, cancer-associated gain-of-function mutations in Rac1 have been identified which contribute to tumor phenotypes and confer resistance to targeted therapies. Deregulated expression/activity of Rac guanine nucleotide exchange factors responsible for Rac activation has been largely associated with a metastatic phenotype and drug resistance. Translating our extensive knowledge in Rac pathway biochemistry into a clinical setting still remains a major challenge; nonetheless, remarkable opportunities for cancer therapeutics arise from promising lead compounds targeting Rac and its effectors.
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Cover Image
Cover Image
The image represents a simplified ‘open’ cell of the gram-positive bacterium Streptomyces coelicolor and selected components of its zinc metabolism. The zinc sensor protein – zinc uptake regulator (Zur) – is shown in metallic blue in the middle, bound to DNA (green) where it works as a transcriptional repressor when zinc levels are adequate. The Zur-regulated high-affinity zinc uptake system ZnuABC is shown in purple. Synthesis of the secreted zincophore coelibactin is also Zur-regulated. Zinc ions are shown as silver balls surrounding the cell, and bound to Zur; for details see pages 983–1001.
The image has been created by Alevtina Mikhaylina with the help of Claudia A. Blindauer and David J. Scanlan.
The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic
Victoria Casado-Medrano, Martin J. Baker, Cynthia Lopez-Haber, Mariana Cooke, Shaofei Wang, Maria J. Caloca, Marcelo G. Kazanietz; The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic. Biochem Soc Trans 20 August 2018; 46 (4): 1003–1012. doi: https://doi.org/10.1042/BST20170519
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