References
PMID:21572392
SMURF1 is an homologous to E6AP C-ter (HECT)-type E3 ubiquitin ligase
SMURF1 performs a crucial role in the regulation of the BMP signalling pathway in both embryonic development and bone remodelling.
PMID:15761148
PARD6A interacts with and is phsophorylated by TGFBR2.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation controls the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
Ubiquitation of RHO1 by Smurf1 leads to disassembly of tight junctions, an important step in EMT.
PMID:22949611
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBR1 binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBR2 phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.
PMID:14657501
SMURF1, but not SMURF2, decreases RHOA level, and this effect is proteasome dependent.
PMID:16472676
Smurf1 could specifically target RhoA but not Cdc42 or Rac1 for degradation.
Smurf1 interacts with the dominant inactive form of RhoA, RhoA N19, which binds constitutively to GEFs in vivo.
Smurf1 also interacts directly with either nucleotide???free or GDP???bound RhoA in vitro;
However, loading with GTPgS inhibits the interaction