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PMID:19018011

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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

Significance

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

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


See also

References

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