On and off: proteasome and TGF-beta signaling.
Transforming growth factor-beta (TGF-beta) signaling mainly relies on the TGF-beta receptor-Smad pathway. Meanwhile, TGF-beta binding to its receptors initiates the degradation of several key components of its signaling pathway. The degradation of these components, including both positive and negative transducers, is mediated by the ubiquitin-proteasome system. Inhibition of the proteasome activity causes accumulation of these components in the cells and modulates TGF-beta signaling in a time-dependent and gene-specific manner. The accelerated degradation of TGF-beta signaling components via the proteasome system has been found in a number of tumors, indicating that dysregulated proteasomal degradation is a novel pathway how tumor cells silence TGF-beta signaling.
Zhang
Fan
F
Haartman Institute and Molecular and Cancer Biology Program, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, P.O. Box 63, FIN-00014 Helsinki, Finland.
Laiho
Marikki
M
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism* / Q000502:physiology; D009369:Neoplasms / Q000209:etiology; D046988:Proteasome Endopeptidase Complex; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex