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Dysregulation of protein modification by ISG15 results in brain cell injury.

Genes & development | Sep 1, 2002

UBP43 (USP18) is a protease that removes the ubiquitin-like modifier ISG15 from conjugated proteins. Here we present the first report of dysregulation of protein ISG15 modification by the generation of UBP43 knockout mice. In the absence of UBP43, brain tissue showed an elevated level of ISG15 conjugates, and cellular necrosis was evident in the ependyma. Such disruption of the blood-brain barrier resulted in severe neurologic disorders. These results demonstrate that UBP43 plays a critical role in maintaining the homeostatic balance of ISG15-conjugated protein, and that regulation of cellular levels of ISG15 protein modification is essential for brain cell function.

Pubmed ID: 12208842 RIS Download

Mesh terms: Animals | Blood-Brain Barrier | Brain | Cytokines | Endopeptidases | Ependyma | Gene Expression | Hydrocephalus | Mice | Mice, Knockout | Necrosis | Phenotype | Protein Processing, Post-Translational | RNA, Messenger | Ubiquitin Thiolesterase | Ubiquitins

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA079849
  • Agency: NCI NIH HHS, Id: CA79849

Mouse Genome Informatics (Data, Gene Annotation)

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