Research ArticleCell Biology

The parkin-coregulated gene product PACRG promotes TNF signaling by stabilizing LUBAC

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Science Signaling  04 Feb 2020:
Vol. 13, Issue 617, eaav1256
DOI: 10.1126/scisignal.aav1256

Stabilizing LUBAC

The parkin-coregulated gene (PACRG) encodes a protein of unknown function and shares a promoter with parkin, which encodes an E3 ubiquitin ligase that induces the degradation of damaged mitochondria and promotes nuclear factor κB (NF-κB) signaling. Meschede et al. found that PACRG played no role in mitophagy in cultured human cells but did promote NF-κB signaling downstream of the tumor necrosis factor (TNF) receptor TNFR1. PACRG was recruited to the TNFR1 signaling complex and protected cells from TNF-induced apoptosis by interacting with and stabilizing the linear ubiquitin chain assembly complex (LUBAC). PACRG functionally substituted for the LUBAC component and adaptor protein SHARPIN. That Parkin and PACRG both promote NF-κB signaling is consistent with previous reports linking polymorphisms in the regulatory regions of both genes with increased susceptibility to infections with intracellular bacterial pathogens.

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