Reactome | The SMAD2/3:SMAD4 complex transfers to the nucleus

The SMAD2/3:SMAD4 complex transfers to the nucleus

Stable Identifier

R-HSA-173488

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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The SMAD2/3:SMAD4 complex transfers to the nucleus

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The phosphorylated R-SMAD:CO-SMAD complex rapidly translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003) where it binds directly to DNA and interacts with a plethora of transcription co-factors. Translocation of SMAD2 and SMAD3 to the nucleus is negatively regulated by ERK-mediated phosphorylation (Kretzschmar et al. 1999). Regulation of target gene expression can be either positive or negative. A classic example of a target gene of the pathway are the genes encoding for I-SMADs. Thus, TGF-beta/SMAD signaling induces the expression of the negative regulators of the pathway (negative feedback loop).

Literature References

PubMed ID	Title	Journal	Year
11294908	Transforming growth factor-beta induces nuclear import of Smad3 in an importin-beta1 and Ran-dependent manner Yoneda, Y, Moustakas, A, Heldin, CH, Kose, S, Kurisaki, A	Mol Biol Cell	2001
20694664	Coupling of dephosphorylation and nuclear export of Smads in TGF-beta signaling Lin, X, Feng, XH, Duan, X, Liang, YY, Dai, F	Methods Mol. Biol.	2010
19114992	Nucleocytoplasmic shuttling of Smad proteins Hill, CS	Cell Res.	2009
12592392	An extended bipartite nuclear localization signal in Smad4 is required for its nuclear import and transcriptional activity Lodish, HF, Latek, R, Xiao, Z	Oncogene	2003
10934479	The nuclear import function of Smad2 is masked by SARA and unmasked by TGFbeta-dependent phosphorylation Massague, J, Xu, L, Chen, YG	Nat Cell Biol	2000
16260601	Kinetic analysis of Smad nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor beta-dependent nuclear accumulation of Smads Hill, CS, Schmierer, B	Mol Cell Biol	2005