title: The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu.
abstract: 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.
authors.affiliation: Institute for Human Genetics, Medical School, University of Mainz, 55122 Mainz, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Schweiger
authors.affiliation: German Center for Neurodegenerative Diseases, 53127 Bonn, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dorn
authors.affiliation: Department of Dermatology, Charité University Hospital, 10117 Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, 6020 Innsbruck, Austria, and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Köhler
authors.affiliation: German Center for Neurodegenerative Diseases, 53127 Bonn, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Matthes
authors.affiliation: Max Delbrück Center for Molecular Medicine, 13125 Berlin-Buch, Germany.
authors.forename: Eva-Christina
authors.initials: EC
authors.lastname: Müller
authors.affiliation: Max Delbrück Center for Molecular Medicine, 13125 Berlin-Buch, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Wanker
authors.affiliation: Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, 6020 Innsbruck, Austria, and.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schneider
authors.affiliation: German Center for Neurodegenerative Diseases, 53127 Bonn, Germany,. Electronic address: sybille.krauss@dzne.de.
authors.forename: Sybille
authors.initials: S
authors.lastname: Krauß
mesh_terms: D002384:Catalysis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D008868:Microtubule Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry*; D054875:Ubiquitination; D000074290:Zinc Finger Protein Gli3
chemical_list: D017931:DNA Primers; C065683:GLI3 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C509239:SHH protein, human; D014157:Transcription Factors; D025801:Ubiquitin; D000074290:Zinc Finger Protein Gli3; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; C496588:STK36 protein, human; D046988:Proteasome Endopeptidase Complex; D008239:Lysine
keywords: Cancer Biology; Fu; GLI3; MID1; Proteasomal Cleavage; Proteasome; Protein Phosphatase 2 (PP2A); Signal transduction; Ubiquitination