Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling.
Effects of the cytokine TGF-beta can be dampened by E3 ubiquitin ligases that target specific Smads, the TGF-beta signal transducers, for proteolytic destruction. Two papers in this issue of Cell highlight the importance of this mechanism in regulating the in vivo effects of TGF-beta. The first paper identifies and characterizes a novel Smad4 ubiquitin ligase, and the second paper redefines the role of a previously identified Smad1 ubiquitin ligase, Smurf-1 (Dupont et al., 2005; Yamashita et al., 2005).
Datto
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Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Wang
X-F
XF
D000818:Animals; D036703:Blastula / Q000378:metabolism; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D052004:Bone Morphogenetic Protein Receptors; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047109:Fetal Development / Q000502:physiology; D005855:Germ Layers / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048730:MAP Kinase Kinase Kinase 2 / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011489:Protein Denaturation / Q000502:physiology; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
D004268:DNA-Binding Proteins; D017978:Receptors, Growth Factor; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C492381:Smurf1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D048031:JNK Mitogen-Activated Protein Kinases; D048730:MAP Kinase Kinase Kinase 2; D052004:Bone Morphogenetic Protein Receptors