Research ArticleCell Biology

TIM Family Proteins Promote the Lysosomal Degradation of the Nuclear Receptor NUR77

Science Signaling  11 Dec 2012:
Vol. 5, Issue 254, pp. ra90
DOI: 10.1126/scisignal.2003200

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Delivered to the Lysosome by TIM

The orphan nuclear receptor NUR77 promotes cell death in the kidney after injury. Balasubramanian et al. identified the TIM (T cell immunoglobulin and mucin domain) family of cell-surface receptors as binding partners of NUR77. TIM proteins inhibited the transactivation function of NUR77 and also promoted its lysosomal degradation, which for TIM-1 required the phosphatidylserine-binding pocket and clathrin-mediated endocytosis. In an in vitro model of ischemic injury with kidney epithelial cells, TIM-1 enhanced cell survival by decreasing the abundance of NUR77. Thus, strategies that increase the abundance of the TIM-1 could ameliorate cell death after kidney injury.