The ubiquitin-like protein FAT10 mediates NF-kappaB activation.

ABSTRACT: NF-kappaB is a central mediator of innate immunity and contributes to the pathogenesis of several renal diseases. FAT10 is a TNF-alpha-inducible ubiquitin-like protein with a putative role in immune response, but whether FAT10 participates in TNF-alpha-induced NF-kappaB activation is unknown. Here, using renal tubular epithelial cells (RTECs) derived from FAT10(-/-) and FAT10(+/+) mice, we observed that FAT10 deficiency abrogated TNF-alpha-induced NF-kappaB activation and reduced the induction of NF-kappaB-regulated genes. Despite normal IkBalpha degradation and polyubiquitination, FAT10 deficiency impaired TNF-alpha-induced IkBalpha degradation and nuclear translocation of p65 in RTECs, suggesting defective proteasomal degradation of polyubiquitinated IkBalpha. In addition, FAT10 deficien

SUBMITTER: Gong P 

PROVIDER: S-EPMC2834541 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature