How ERK1/2 Activation Controls Cell Proliferation and Cell Death Is Subcellular Localization the Answer?
By Y. Mebratu, Y. Tesfaigzi. Cell Cycle, 2009
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Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) are members of the mitogen-activated protein kinase super family that can mediate cell proliferation and apoptosis. The Ras–Raf–MEK–ERK signaling cascade controlling cell proliferation has been well studied but the mechanisms involved in ERK1/2-mediated cell death are largely unknown. This review focuses on recent papers that define ERK1/2 translocation to the nucleus and the proteins involved in the cytosolic retention of activated ERK1/2. Cytosolic retention of ERK1/2 denies access to the transcription factor substrates that are responsible for the mitogenic response. In addition, cytosolic ERK1/2, besides inhibiting survival and proliferative signals in the nucleus, potentiates the catalytic activity of some proapoptotic proteins such as DAP kinase in the cytoplasm. Studies that further define the function of cytosolic ERK1/2 and its cytosolic substrates that enhance cell death will be essential to harness this pathway for developing effective treatments for cancer and chronic inflammatory diseases.
Subfields: Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/1deb40660cbd534381d8a86f36d11fcb96b271f8
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Citations in the corpus
- Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging (2011, background): “These pathways relay this information through interactions with various other proteins to the nucleus to control gene expression [1-13].”
- Mechanistic Basis of Antimicrobial Actions of Silver Nanoparticles (2016, background): “There is possible involvement of protein acting downstream to ERK in modulation of cell cycle and apoptosis (Zhang and Liu, 2002; Mebratu and Tesfaigzi, 2009).”
- The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. (2011, background): “One way for the regulation of transcription factors by MAPKs is via the modulation of their subcellular localization [181].”
- Targeting the Mitogen-Activated Protein Kinase RAS-RAF Signaling Pathway in Cancer Therapy (2012, background): “Once activated, ERK1/ERK2 broadly phosphorylate several nuclear and cytoplasmic effector genes involved in diverse cellular responses such as cell proliferation, survival, differentiation, motility and angiogenesis [19-21].”