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The Role of Ubiquitination to Determine Non-Smad Signaling Responses. Ubiquitination is a posttranslational modification of proteins which acts as a key regulator of their function as well as fate. We have recently reported transforming growth factor β (TGFβ)-induced activation of non-Smad signaling responses through a specific Lys63-linked polyubiquitination of TGFβ type I receptor and TGFβ-associated kinase 1 (TAK1) that are utilized to specify cellular responses in cancer cells. This chapter gives a brief introduction of the biological importance of ubiquitination of proteins, the methods we have used for detecting new partners in the TGFβ signaling pathway and for performing ubiquitination assays.

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