Phosphorylation of the mRNA cap-binding protein eIF4E and cancer |
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| Affiliation: | 1. Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China;2. Department of Respiratory and Critical Care Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou, China;1. Departments of Biochemistry and Oncology, McGill University, Montreal, Quebec, Canada;2. Pathology Department, Vall d’Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain;3. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Spain;4. Goodman Cancer Research Center, McGill University, Montreal, Quebec, Canada;1. Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany;1. Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China;2. The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China;3. Department of Biology Science and Technology, Baotou Teacher''s College, Baotou, 014030, China;4. Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China;5. Department of Thoracic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266035, China;6. Department of Pharmaceutical Analysis, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China |
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| Abstract: | Dysregulated protein synthesis is frequently involved in oncogenesis and cancer progression. Translation initiation is thought to be the rate-limiting step in protein synthesis, and the mRNA 5′ cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) is a pivotal factor that initiates translation. The activities of eIF4E are regulated at multiple levels, one of which is through its phosphorylation at Serine 209 by the mitogen-activated protein kinase-interacting kinases (MNKs, including MNK1 and MNK2). Benefiting from novel mouse genetic tools and pharmacological MNK inhibitors, our understanding of a role for eIF4E phosphorylation in tumor biology and cancer therapy has greatly evolved in recent years. Importantly, recent studies have found that the level of eIF4E phosphorylation is frequently upregulated in a wide variety of human cancer types, and phosphorylation of eIF4E drives a number of important processes in cancer biology, including cell transformation, proliferation, apoptosis, metastasis and angiogenesis. The MNK-eIF4E axis is being assessed as a therapeutic target either alone or in combination with other therapies in different cancer models. As novel MNK inhibitors are being developed, experimental studies bring new hope to cure human cancers that are not responsive to traditional therapies. Herein we review recent progress on our understanding of a mechanistic role for phosphorylation of eIF4E in cancer biology and therapy. |
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