Journal Article DZNE-2020-03971

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The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu.

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2014
Soc.60645 Bethesda, Md.

The journal of biological chemistry 289(46), 31805-31817 () [10.1074/jbc.M113.541219]

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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.

Keyword(s): Protein Serine-Threonine Kinases: metabolism (MeSH) ; Catalysis (MeSH) ; Cell Line, Tumor (MeSH) ; Cell Nucleus: metabolism (MeSH) ; DNA Primers (MeSH) ; Gene Expression Regulation, Neoplastic (MeSH) ; HeLa Cells (MeSH) ; Hedgehog Proteins: metabolism (MeSH) ; Humans (MeSH) ; Kruppel-Like Transcription Factors: metabolism (MeSH) ; Lysine: chemistry (MeSH) ; Microtubule Proteins: metabolism (MeSH) ; Nerve Tissue Proteins: metabolism (MeSH) ; Nuclear Proteins: metabolism (MeSH) ; Proteasome Endopeptidase Complex: metabolism (MeSH) ; Protein-Serine-Threonine Kinases: metabolism (MeSH) ; Signal Transduction (MeSH) ; Transcription Factors: metabolism (MeSH) ; Ubiquitin: chemistry (MeSH) ; Ubiquitin-Protein Ligases: chemistry (MeSH) ; Ubiquitination (MeSH) ; Zinc Finger Protein Gli3 (MeSH) ; DNA Primers ; GLI3 protein, human ; Hedgehog Proteins ; Kruppel-Like Transcription Factors ; Microtubule Proteins ; Nerve Tissue Proteins ; Nuclear Proteins ; SHH protein, human ; Transcription Factors ; Ubiquitin ; Zinc Finger Protein Gli3 ; Mid1 protein, human ; Ubiquitin-Protein Ligases ; Protein-Serine-Threonine Kinases ; STK36 protein, human ; Proteasome Endopeptidase Complex ; Lysine

Classification:

Contributing Institute(s):
  1. Regulatory RNA-protein interaction in neurodegenerative diseases (AG Krauß)
Research Program(s):
  1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2014
Database coverage:
Medline ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection
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BN DZNE-AG Krauß
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 Record created 2020-02-18, last modified 2024-03-21


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