Dataset Information

USP11 augments TGFβ signalling by deubiquitylating ALK5.

ABSTRACT: The TGFβ receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFβ signals, negatively regulates the TGFβ pathway by recruiting E3 ubiquitin ligases and targeting TGFβ receptors for ubiquitin-mediated degradation. In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFβ signalling and can override the negative effects of SMAD7. USP11 interacts with and deubiquitylates the type I TGFβ receptor (ALK5), resulting in enhanced TGFβ-induced gene transcription. The deubiquitylase activity of USP11 is required to enhance TGFβ-induced gene transcription. RNAi-mediated depletion of USP11 results in inhibition of TGFβ-induced SMAD2/3 phosphorylation and TGFβ-mediated transcriptional responses. Central to TGFβ pathway signalling in early embryogenesis and carcinogenesis is TGFβ-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFβ-induced epithelial to mesenchymal transition.

SUBMITTER: Al-Salihi MA

PROVIDER: S-EPMC3390794 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

USP11 augments TGFβ signalling by deubiquitylating ALK5.

Al-Salihi Mazin A MA Herhaus Lina L Macartney Thomas T Sapkota Gopal P GP

Open biology 20120601 6

The TGFβ receptors signal through phosphorylation and nuclear translocation of SMAD2/3. SMAD7, a transcriptional target of TGFβ signals, negatively regulates the TGFβ pathway by recruiting E3 ubiquitin ligases and targeting TGFβ receptors for ubiquitin-mediated degradation. In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFβ signalling and can override the negative effects of SMAD7. USP11 interacts with and deubiquitylates the type I TGFβ re ...[more]

PMID: 22773947

Similar Datasets

Project description:The sympathetic system is involved in the arterial diseases, but its mechanism remains poorly understood. The present study aimed to explore the impact of the sympathetic neurotransmitter norepinephrine (NE) on transforming growth factor (TGF) β signaling and the role of NE in aortic remodeling. Guanethidine was used to induce a regional chemical sympathetic denervation (CSD) in angiotensin II (AngII) and β‑aminopropionitrile (BAPN)‑induced aortic aneurysm models. The diameter of the aorta was measured, and elastic fiber staining was performed. TGFβ type I receptor kinase (ALK5) expression in rat aortic NE‑treated vascular smooth muscle cells (VSMCs) was detected by reverse transcription‑quantitative PCR and western blotting. The effects of NE and ALK5 overexpression on migration, proliferation, apoptosis and TGFβ signaling were also evaluated. Furthermore, adrenergic receptor blockers were used to determine which receptor was involved in the modulation on TGFβ signaling by NE. The results of the present study demonstrated that CSD protected rats from AngII+BAPN‑induced aortic remodeling and aneurysm formation. Compared with the control group, NE inhibited VSMC proliferation and migration, but promoted apoptosis by suppressing ALK5 expression, reversing the effects of TGFβ signaling through the suppression of the SMAD‑dependent canonical pathway and promotion of the non‑canonical pathway. These effects were prevented by ALK5 overexpression. The inhibition of α‑ or β‑adrenergic receptors alleviated the NE‑mediated suppression of ALK5 expression. In conclusion, regional CSD protected rats from aortic aneurysm. NE inhibited SMAD2/3‑dependent TGFβ signaling by suppressing ALK5 expression, which may serve an important role in VSMC biological functions. Both α‑ and β‑adrenergic receptors were involved in the regulation of ALK5 expression by NE. Abnormal sympathetic innervation of the aorta may be used as a therapeutic target in aortic diseases.

Dataset Information

USP11 augments TGFβ signalling by deubiquitylating ALK5.

Publications

USP11 augments TGFβ signalling by deubiquitylating ALK5.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets