Rab Proteins, Intracellular Transport and Cancer

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Klin Onkol 2016; 29(Suppl 4): 31-39. DOI: 10.14735/amko20164S31.

Background: Rab proteins are small monomeric enzymes which belong to the large Ras protein superfamily and allow hydrolysis of guanosine triphosphate (GTP) to guanosine (GDP). Up to now more than 60 proteins have been described that act primarily as regulators of intracellular transport. Rab GTPases are mostly located at the intracellular membranes, where they provide connections to motor proteins and to the cytoskeleton and control various steps of the traffic pathways including the formation and movement of vesicles or membrane fusion controlling secretion, endocytosis, recycling and degradation of proteins. Today, the deregulated expression of Rab protein is discussed in different types of malignancies. The number of identified diseases associated with mutations in Rab proteins or their cooperating partners increases and the evidence for the involvement of Rab to the human pathologies such as the immune failure, obesity and diabetes, Alzheimer‘s disease or hereditary genetic diseases is growing. The malfunctions of Rab proteins caused by mutations or aberrant posttranslational modifications lead to changes in the protein and vesicle trafficking, which play a crucial role in the formation and development of cancer and the deregulation of Rab expression frequently influences the migration, invasion, proliferation and drug resistance of the tumor cells. Aims: This article summarizes the main functions of Rab proteins in the cells, describes the mechanism of their activity and focuses on the current knowledge about the roles of these GTPases in carcinogenesis.

http://dx.doi.org/10.14735/amko20164S31

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