6m64
From Proteopedia
Crystal structure of SMAD2 in complex with CBP
Structural highlights
FunctionSMAD2_HUMAN Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.[1] [2] [3] [4] [5] Publication Abstract from PubMedTransforming growth factor-beta (TGF-beta) proteins regulate multiple cellular functions, including cell proliferation, apoptosis, and extracellular matrix formation. The dysregulation of TGF-beta signaling causes diseases such as cancer and fibrosis, and therefore, understanding the biochemical basis of TGF-beta signal transduction is important for elucidating pathogenic mechanisms in these diseases. SMAD proteins are transcription factors that mediate TGF-beta signaling-dependent gene expression. The transcriptional coactivator CBP directly interacts with the MH2 domains of SMAD2 to activate SMAD complex-dependent gene expression. Here, we report the structural basis for CBP recognition by SMAD2. The crystal structures of the SMAD2 MH2 domain in complex with the SMAD2-binding region of CBP showed that CBP forms an amphiphilic helix on the hydrophobic surface of SMAD2. The expression of a mutated CBP peptide that showed increased SMAD2 binding repressed SMAD2-dependent gene expression in response to TGF-beta signaling in cultured cells. Disrupting the interaction between SMAD2 and CBP may therefore be a promising strategy for suppressing SMAD-dependent gene expression. Structural basis for transcriptional coactivator recognition by SMAD2 in TGF-beta signaling.,Miyazono KI, Ito T, Fukatsu Y, Wada H, Kurisaki A, Tanokura M Sci Signal. 2020 Dec 15;13(662):eabb9043. doi: 10.1126/scisignal.abb9043. PMID:33323411[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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