To Ub or not to Ub: a regulatory question in TGF-β signaling.

The transforming growth factor β (TGF-β) superfamily controls a wide spectrum of biological processes in metazoans, including cell proliferation, apoptosis, differentiation, cell-fate determination, and embryonic development. Deregulation of TGF-β-Smad signaling contributes to developmental anomalies and a variety of disorders and diseases such as tumorigenesis, fibrotic disorders, and immune diseases. In cancer, TGF-β has dual effects through its antiproliferative and prometastatic actions. At the cellular level, TGF-β functions mainly through the canonical Smad-dependent pathway in a cell type-specific and context-dependent manner. Accumulating evidence has demonstrated that ubiquitination plays a vital role in regulating TGF-β-Smad signaling. We summarize current progress on ubiquitination (Ub) and the ubiquitin ligases that regulate TGF-β-Smad signaling.