RGD Reference Report - Identification of the ubiquitin-like domain of midnolin as a new glucokinase interaction partner. - Rat Genome Database

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Identification of the ubiquitin-like domain of midnolin as a new glucokinase interaction partner.

Authors: Hofmeister-Brix, A  Kollmann, K  Langer, S  Schultz, J  Lenzen, S  Baltrusch, S 
Citation: Hofmeister-Brix A, etal., J Biol Chem. 2013 Dec 13;288(50):35824-39. doi: 10.1074/jbc.M113.526632. Epub 2013 Nov 1.
RGD ID: 8655525
Pubmed: PMID:24187134   (View Abstract at PubMed)
PMCID: PMC3861633   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M113.526632   (Journal Full-text)

Glucokinase acts as a glucose sensor in pancreatic beta cells. Its posttranslational regulation is important but not yet fully understood. Therefore, a pancreatic islet yeast two-hybrid library was produced and searched for glucokinase-binding proteins. A protein sequence containing a full-length ubiquitin-like domain was identified to interact with glucokinase. Mammalian two-hybrid and fluorescence resonance energy transfer analyses confirmed the interaction between glucokinase and the ubiquitin-like domain in insulin-secreting MIN6 cells and revealed the highest binding affinity at low glucose. Overexpression of parkin, an ubiquitin E3 ligase exhibiting an ubiquitin-like domain with high homology to the identified, diminished insulin secretion in MIN6 cells but had only some effect on glucokinase activity. Overexpression of the elucidated ubiquitin-like domain or midnolin, containing exactly this ubiquitin-like domain, significantly reduced both intrinsic glucokinase activity and glucose-induced insulin secretion. Midnolin has been to date classified as a nucleolar protein regulating mouse development. However, we could not confirm localization of midnolin in nucleoli. Fluorescence microscopy analyses revealed localization of midnolin in nucleus and cytoplasm and co-localization with glucokinase in pancreatic beta cells. In addition we could show that midnolin gene expression in pancreatic islets is up-regulated at low glucose and that the midnolin protein is highly expressed in pancreatic beta cells and also in liver, muscle, and brain of the adult mouse and cell lines of human and rat origin. Thus, the results of our study suggest that midnolin plays a role in cellular signaling of adult tissues and regulates glucokinase enzyme activity in pancreatic beta cells.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of insulin secretion acts_upstream_of_or_withinIDA 8655525PMID:24187134MGI 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleolus NOT|located_inIDA 8655525PMID:24187134MGI 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
kinase binding enablesIPIUniProtKB:P355578655525PMID:24187134MGI 

Objects Annotated

Genes (Rattus norvegicus)
Midn  (midnolin)


Additional Information