Ubiquitin Ligase (E3; SMURF)
When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction[1]. Smad ubiquitylation regulatory factor-1 (Smurf1; EC 6.3.2.19) has been identified as a HECT type E3, and has been related to multiple biological processes such as cell growth and migration, and explored for several physiological functions in bone formation, embryonic development, and tumorigenesis[2]. Smurf1 was identified as a negative regulator of BMP signaling, as it ubiquitinates Smad1 and Smad5 for proteasomal degradation to prevent the mild BMP signal from bursting into an overwhelming consequence. CDK8-mediated phosphorylation of Smad1/5 facilitates the transcriptional complex in activating its target genes. Furthermore, it promotes GSK3-mediated phosphorylation of Smad1/5, which leads to the capture of Smad1/5 by Smurf1[3].
[1] E. Aragón et al. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev. 2011 Jun 15;25(12):1275-88.
[2] Y. Cao et al.A Smurf1 tale: function and regulation of an ubiquitin ligase in multiple cellular networks. Cell Mol Life Sci. 2013 Jul;70(13):2305-17.
[3] Y. Cao et al. Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradation. Sci Rep. 2014 May 14;4:4965.
Axon ID | Name | Description | From price | |
---|---|---|---|---|
2426 | SMURF1 inhibitor A01 | Inhibitor of E3 ubiquitin-protein ligase SMURF1 | €115.00 |