Adaptor proteins and ubiquinators in TGF-β signaling

The emergence of research analyzing the TGF-β signaling pathway and its role in stem cell plasticity and differentiation has been a source of new insights into multiple cancers. TGF-β signaling mediator Smads are tightly dependent on modulation by adaptor proteins, such as ELF, SARA, filamin, and crkl as well as ubiquitinators, such as PRAJA and SMURFs. Despite widespread inactivation of the TGF-β pathway in gastrointestinal tumors, only a fraction of sporadic tumors exhibit inactivating mutations in early tumor formation, which suggests a role for the modulation of TGF-β signals by stem/progenitor cell proteins, such as ELF and PRAJA. Delineating these key interactions of the TGF-β signaling pathway could yield powerful new therapeutics aimed at treating hitherto difficult to treat cancers.