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].