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

Stable Identifier
R-HSA-173481
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
10485843 The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling

Luo, K, Stroschein, SL, Wang, W, Chen, D, Martens, E, Zhou, S, Zhou, Q

Genes Dev 1999
10531062 Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein

Stroschein, SL, Wang, W, Zhou, S, Zhou, Q, Luo, K

Science 1999
10549282 Interaction of the Ski oncoprotein with Smad3 regulates TGF-beta signaling

Sun, Y, Liu, X, Eaton, EN, Lane, WS, Lodish, HF, Weinberg, RA

Mol Cell 1999
11389444 TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation

Bonni, S, Wang, HR, Causing, CG, Kavsak, P, Stroschein, SL, Luo, K, Wrana, JL

Nat Cell Biol 2001
10535941 SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor beta signaling

Sun, Y, Liu, X, Ng-Eaton, E, Lodish, HF, Weinberg, RA

Proc Natl Acad Sci U S A 1999
Participants
Participant Of
Orthologous Events
Authored
Reviewed