Reactome | Degradation of Ub-SMAD7

Degradation of Ub-SMAD7

Stable Identifier

R-HSA-2186780

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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After ubiquitination by RNF111 (Arkadia), ubiquitinated SMAD7 is degraded in a proteasome dependent way. Therefore, RNF111 has a positive effect on transcription initiated by TGF-beta signaling. However, TGF-beta signaling ultimately results in a decrease of RNF111 mRNA level, enabling negative-feedback regulation of TGF-beta signal by SMAD7.
RNF111 may fine tune the duration of cellular response to TGF-beta signal. Initially, RNF111 may enable signal propagation by inhibiting negative regulators of TGF-beta signaling, SKI/SKIL and SMAD7. Subsequent negative regulation of RNF111 expression by TGF-beta may allow the signaling cascade to be turned off (Koinuma et al. 2003).

Literature References

PubMed ID	Title	Journal	Year
14657019	Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7 Miyazono, K, Goto, K, Shinozaki, M, Imamura, T, Nukiwa, T, Komuro, A, Ebina, M, Miyazawa, K, Saitoh, M, Hanyu, A, Koinuma, D	EMBO J	2003