Reactome | SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling

SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling

Stable Identifier

R-HSA-173481

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling

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SKI and SKIL (SNO) are able to recruit NCOR and possibly other transcriptional repressors to SMAD2/3:SMAD4 complex, inhibiting SMAD2/3:SMAD4-mediated transcription (Sun et al. 1999, Luo et al. 1999, Strochein et al. 1999). Experimental findings suggest that SMAD2 and SMAD3 may target SKI and SKIL for degradation (Strochein et al. 1999, Sun et al. 1999 PNAS, Bonni et al. 2001), and that the ratio of SMAD2/3 and SKI/SKIL determines the outcome (inhibition of SMAD2/3:SMAD4-mediated transcription or degradation of SKI/SKIL). SKI and SKIL are overexpressed in various cancer types and their oncogenic effect is connected with their ability to inhibit signaling by TGF-beta receptor complex.

Literature References

PubMed ID	Title	Journal	Year
10531062	Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein Zhou, Q, Luo, K, Zhou, S, Stroschein, SL, Wang, W	Science	1999
10485843	The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling Zhou, Q, Luo, K, Zhou, S, Martens, E, Stroschein, SL, Chen, D, Wang, W	Genes Dev	1999
10549282	Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling Sun, Y, Liu, X, Lodish, HF, Eaton, EN, Lane, WS, Weinberg, RA	Mol Cell	1999
11389444	TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation Wrana, JL, Luo, K, Bonni, S, Wang, HR, Stroschein, SL, Causing, CG, Kavsak, P	Nat Cell Biol	2001
10535941	SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor beta signaling Lodish, HF, Ng-Eaton, E, Sun, Y, Liu, X, Weinberg, RA	Proc Natl Acad Sci U S A	1999