Receptor-activated transcription factors and beyond: multiple modes of Smad2/3-dependent transmission of TGF-ß signaling.
J Biol Chem
; 300(5): 107256, 2024 May.
Article
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| MEDLINE
| ID: mdl-38569937
ABSTRACT
Transforming growth factor ß (TGF-ß) is a pleiotropic cytokine that is widely distributed throughout the body. Its receptor proteins, TGF-ß type I and type II receptors, are also ubiquitously expressed. Therefore, the regulation of various signaling outputs in a context-dependent manner is a critical issue in this field. Smad proteins were originally identified as signal-activated transcription factors similar to signal transducer and activator of transcription proteins. Smads are activated by serine phosphorylation mediated by intrinsic receptor dual specificity kinases of the TGF-ß family, indicating that Smads are receptor-restricted effector molecules downstream of ligands of the TGF-ß family. Smad proteins have other functions in addition to transcriptional regulation, including post-transcriptional regulation of micro-RNA processing, pre-mRNA splicing, and m6A methylation. Recent technical advances have identified a novel landscape of Smad-dependent signal transduction, including regulation of mitochondrial function without involving regulation of gene expression. Therefore, Smad proteins are receptor-activated transcription factors and also act as intracellular signaling modulators with multiple modes of function. In this review, we discuss the role of Smad proteins as receptor-activated transcription factors and beyond. We also describe the functional differences between Smad2 and Smad3, two receptor-activated Smad proteins downstream of TGF-ß, activin, myostatin, growth and differentiation factor (GDF) 11, and Nodal.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Factor de Crecimiento Transformador beta
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Proteína Smad2
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Proteína smad3
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2024
Tipo del documento:
Article