How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer?
Top Cited Papers
- 15 April 2009
- journal article
- review article
- Published by Informa UK Limited in Cell Cycle
- Vol. 8 (8), 1168-1175
- https://doi.org/10.4161/cc.8.8.8147
Abstract
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.Keywords
This publication has 100 references indexed in Scilit:
- Protein Kinase B/Akt Binds and Phosphorylates PED/PEA-15, Stabilizing Its Antiapoptotic ActionMolecular and Cellular Biology, 2003
- Fas engagement induces neurite growth through ERK activation and p35 upregulationNature, 2003
- Evidence That Inhibition of p44/42 Mitogen-activated Protein Kinase Signaling Is a Factor in Proteasome Inhibitor-mediated ApoptosisPublished by Elsevier BV ,2002
- Mutations of the BRAF gene in human cancerNature, 2002
- T cell–mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitisJCI Insight, 2000
- Distantly Related Cousins of MAP Kinase: Biochemical Properties and Possible Physiological FunctionsBiochemical and Biophysical Research Communications, 1999
- Defective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout MiceScience, 1999
- DNA Damage in Deoxynucleosides and Oligonucleotides Treated with PeroxynitriteChemical Research in Toxicology, 1999
- ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGFCell, 1991
- Tissue Destruction by NeutrophilsThe New England Journal of Medicine, 1989