Ubiquitin chains in the ladder of MAPK signaling.
With a better understanding of the cellular stress response, it has become evident that catalytic modules consisting of kinases that mediate the activation of downstream effector components are subject to multiple layers of regulation. Such regulatory mechanisms are not limited to those involving scaffold proteins or protein phosphatases, and they appear to include a growing number of modifications by ubiquitin and ubiquitin-like proteins. The role of ubiquitin in the regulation of mitogen-activated protein kinase (MAPK) emerges as a paradigm for understanding the role of ubiquitination in regulating other signal transduction pathways. Ubiquitination influences signal diversification and limits the duration of the signal through its role in the assembly of protein kinase complexes, subcellular localization, and the actual degradation of the kinase or its substrate. This review summarizes our current understanding of the roles of ubiquitin in regulating MAPK signaling.
Laine
Aaron
A
Signal Transduction Program, The Burnham Institute, La Jolla, CA 92037, USA.
Ronai
Ze'ev
Z
D000818:Animals; D010450:Endopeptidases / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000145:classification / Q000502:physiology; D046912:Multiprotein Complexes; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D013312:Stress, Physiological / Q000201:enzymology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000502:physiology; D025801:Ubiquitin / Q000502:physiology*
D046912:Multiprotein Complexes; D016755:Proto-Oncogene Proteins c-jun; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D025801:Ubiquitin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010450:Endopeptidases