PMID:19018011

Citation	Hoover, LL and Kubalak, SW (2008) Holding their own: the noncanonical roles of Smad proteins. Sci Signal 1:pe48
Abstract	The identification of Smads as protein transcription factors in 1995 led to elucidation of the canonical transforming growth factor-beta (TGF-beta) signaling pathway. In the years that have followed, nuances of the pathway have been realized, and the once-simple scheme of ligand to receptor to activated transcription factor is now understood to be highly regulated at each step and riddled with crosstalk from other pathways. The Smads are also recognized as important players outside of canonical TGF-beta-dependent signaling and are responsible for regulating diverse cellular processes. New evidence suggests that Smad7 plays an integral role in maintaining cell-cell adhesion through direct regulation of beta-catenin. Receptor-activated Smads regulate the processing of a subset of microRNAs, particularly miR-21. The number of reports demonstrating the interactions of Smads with proteins outside of canonical TGF-beta signaling is increasing, although the functional relevance of these interactions is not known. Investigating these interactions will likely yield more evidence that Smads serve important and diverse purposes beyond their original reported function as signal transducers in the TGF-beta pathway.
Links	PubMed PMC2913314 Online version:10.1126/scisignal.146pe48
Keywords	Animals; Cell Adhesion/physiology; Humans; MicroRNAs/metabolism; Models, Biological; Phosphorylation; RNA Processing, Post-Transcriptional; Signal Transduction/physiology; Smad Proteins/physiology; Transforming Growth Factor beta/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SMAD9	involved_in	GO:0030509: BMP signaling pathway	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD6	enables	GO:0140416: transcription regulator inhibitor activity	ECO:0000304: author statement supported by traceable reference used in manual assertion		F	part_of:(GO:0030512)	Seeded From UniProt	complete
HUMAN:TTK	involved_in	GO:0010862: positive regulation of pathway-restricted SMAD protein phosphorylation	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD1	involved_in	GO:0030509: BMP signaling pathway	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD5	involved_in	GO:0030509: BMP signaling pathway	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD1	part_of	GO:0005634: nucleus	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
HUMAN:SMAD1	enables	GO:0030618: transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity	ECO:0000304: author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
HUMAN:SMAD1	involved_in	GO:0031053: primary miRNA processing	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD2	involved_in	GO:0031053: primary miRNA processing	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD2	involved_in	GO:0007369: gastrulation	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD3	involved_in	GO:0042060: wound healing	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD3	involved_in	GO:0031053: primary miRNA processing	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD5	enables	GO:0030618: transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity	ECO:0000304: author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
HUMAN:SMAD5	part_of	GO:0005634: nucleus	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
HUMAN:SMAD6	part_of	GO:0005737: cytoplasm	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
HUMAN:SMAD7	involved_in	GO:0060394: negative regulation of pathway-restricted SMAD protein phosphorylation	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD7	involved_in	GO:0030336: negative regulation of cell migration	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD7	involved_in	GO:0010719: negative regulation of epithelial to mesenchymal transition	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMAD9	enables	GO:0030618: transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity	ECO:0000304: author statement supported by traceable reference used in manual assertion		F		Seeded From UniProt	complete
HUMAN:SMAD9	part_of	GO:0005634: nucleus	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TGFB1	involved_in	GO:0030334: regulation of cell migration	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete

References

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