TIM family proteins promote the lysosomal degradation of the nuclear receptor NUR77

Savithri Balasubramanian, Satya Keerthi Kota, Vijay K. Kuchroo, Benjamin D. Humphreys, Terry B. Strom

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


T cell immunoglobulin and mucin domain (TIM) proteins are cell-surface signaling receptors in T cells and scavenger receptors in antigen-presenting cells and kidney tubular epithelia. Here, we demonstrated a function for TIM proteins in mediating the degradation of NUR77, a nuclear receptor implicated in apoptosis and cell survival. TIM proteins interacted with and mediated the lysosomal degradation of NUR77 in a phosphoinositide 3-kinase-dependent pathway. We also showed dynamic cycling of TIM-1 to and from the cell surface through clathrin-dependent constitutive endocytosis. Blocking this process or mutating the phosphatidylserine-binding pocket in TIM-1 abrogated TIM-1- mediated degradation of NUR77. In an in vitro model of kidney injury, silencing TIM-1 increased NUR77 abundance and decreased epithelial cell survival. These results show that TIM proteins may affect immune cell function and the response of the kidney to injury.

Original languageEnglish
Article numberra90
JournalScience signaling
Issue number254
StatePublished - Dec 11 2012


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