DRAK2 Participates in a Negative Feedback Loop to Control TGF-β/Smads Signaling by Binding to Type I TGF-β Receptor

• DOI: 10.1016/j.celrep.2012.09.028
• Publication Date: 2012-11-29T20:21:06Z
• Authors: Kyung-Min Yang; Wonjoo Kim; Eunjin Bae; Jungsoo Gim; Brian M. Weist; Yunshin Jung; Ja-Shil Hyun; Jennifer B. Herna...; Sun-Hee Leem; Taesung Park; Joon Jeong; Craig M. Walsh; Seong-Jin Kim
• Keywords: 0301 basic medicine; 570; kinase; smad7; QH301-705.5; Molecular Sequence Data; Receptor, Transforming Growth Factor-beta Type I; 610; Breast Neoplasms; Mice, SCID; Protein Serine-Threonine Kinases; Mice; 03 medical and health sciences; human gastric-cancer; Cell Line, Tumor; expression; Animals; Humans; Amino Acid Sequence; Biology (General); RNA, Small Interfering; breast-cancer; degradation; autoimmunity; 16. Peace & justice; HEK293 Cells; Amino Acid Substitution; Bone Morphogenetic Proteins; tumorigenicity; Female; RNA Interference; t-cell apoptosis; protein; Apoptosis Regulatory Proteins; Receptors, Transforming Growth Factor beta; HeLa Cells; Protein Binding

TGF-β1 is a multifunctional cytokine that mediates diverse biological processes. However, the mechanisms by which intracellular signals of are terminated not well understood. Here, we demonstrate DRAK2 serves as TGF-β1-inducible antagonist TGF-β signaling. stimulation rapidly induces expression and enhances endogenous interaction type I receptor with DRAK2, thereby blocking R-Smads recruitment. Depletion markedly augmented intensity extent responses. Furthermore, high level was observed in basal-like HER2-enriched breast tumors cell lines, depletion suppressed tumorigenic ability cancer cells. Thus, these studies define function for an intrinsic participating negative feedback loop to control responses, aberrant increases potential, part, through inhibition tumor suppressor activity.