The E3 Ubiquitin Ligase MID1 Catalyzes Ubiquitination and Cleavage of Fu
Copyright policy )The E3 Ubiquitin Ligase MID1 Catalyzes Ubiquitination and Cleavage of Fu
SHH (Sonic Hedgehog)-GLI signaling plays an important role during embryogenesis and in tumorigenesis. The survival and growth of several types of cancer depend on autonomously activated SHH-GLI signaling. A protein complex containing the ubiquitin ligase MID1 and protein phosphatase 2A regulates the nuclear localization and transcriptional activity of GLI3, a transcriptional effector molecule of SHH, in cancer cell lines with autonomously activated SHH signaling. However, the exact molecular mechanisms that mediate the interaction between MID1 and GLI3 remained unknown. Here, we show that MID1 catalyzes the ubiquitination and proteasomal cleavage of the GLI3 regulator Fu. Our data suggest that Fu ubiquitination and cleavage is one of the key elements connecting the MID1-PP2A protein complex with GLI3 activity control.
metabolism [Kruppel-Like Transcription Factors], Proteasome Endopeptidase Complex, STK36 protein, human, Ubiquitin-Protein Ligases, metabolism [Microtubule Proteins], Kruppel-Like Transcription Factors, Nerve Tissue Proteins, Protein Serine-Threonine Kinases, chemistry [Ubiquitin-Protein Ligases], Catalysis, metabolism [Protein Serine-Threonine Kinases], Zinc Finger Protein Gli3, Cell Line, Tumor, Humans, metabolism [Transcription Factors], Hedgehog Proteins, metabolism [Proteasome Endopeptidase Complex], metabolism [Cell Nucleus], chemistry [Lysine], DNA Primers, Cell Nucleus, ddc:610, metabolism [Nerve Tissue Proteins], Ubiquitin, Lysine, metabolism [Protein-Serine-Threonine Kinases], Ubiquitination, Nuclear Proteins, chemistry [Ubiquitin], Protein-Serine-Threonine Kinases, Gene Expression Regulation, Neoplastic, GLI3 protein, human, Microtubule Proteins, SHH protein, human, metabolism [Hedgehog Proteins], Function and Dysfunction of the Nervous System, metabolism [Nuclear Proteins], Mid1 protein, human, HeLa Cells, Signal Transduction, Transcription Factors, ddc: ddc:540
metabolism [Kruppel-Like Transcription Factors], Proteasome Endopeptidase Complex, STK36 protein, human, Ubiquitin-Protein Ligases, metabolism [Microtubule Proteins], Kruppel-Like Transcription Factors, Nerve Tissue Proteins, Protein Serine-Threonine Kinases, chemistry [Ubiquitin-Protein Ligases], Catalysis, metabolism [Protein Serine-Threonine Kinases], Zinc Finger Protein Gli3, Cell Line, Tumor, Humans, metabolism [Transcription Factors], Hedgehog Proteins, metabolism [Proteasome Endopeptidase Complex], metabolism [Cell Nucleus], chemistry [Lysine], DNA Primers, Cell Nucleus, ddc:610, metabolism [Nerve Tissue Proteins], Ubiquitin, Lysine, metabolism [Protein-Serine-Threonine Kinases], Ubiquitination, Nuclear Proteins, chemistry [Ubiquitin], Protein-Serine-Threonine Kinases, Gene Expression Regulation, Neoplastic, GLI3 protein, human, Microtubule Proteins, SHH protein, human, metabolism [Hedgehog Proteins], Function and Dysfunction of the Nervous System, metabolism [Nuclear Proteins], Mid1 protein, human, HeLa Cells, Signal Transduction, Transcription Factors, ddc: ddc:540
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