Parkin paves the path to antitumor immunity: Expanding Parkin’s role as a tumor suppressor
Hyungsoo Kim, Ze’ev A. Ronai
Hyungsoo Kim, Ze’ev A. Ronai
Published November 15, 2024
Citation Information: J Clin Invest. 2024;134(22):e185838. https://doi.org/10.1172/JCI185838.
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Commentary

Parkin paves the path to antitumor immunity: Expanding Parkin’s role as a tumor suppressor

Abstract

Parkin, a ring-between-ring-type E3 ubiquitin ligase, first shown to play a critical role in autosomal recessive juvenile Parkinsonism, has recently emerged as a key player in cancer biology. Parkin is now known to serve as a tumor suppressor, and its deregulation frequently promotes tumorigenesis. In this issue of the JCI, Perego et al. expand that role by showing that Parkin expression stimulated an interferon (IFN) response to modulate CD8+ T cell activity. These findings suggest that, in addition to directly inhibiting tumor progression, Parkin enhances antitumor immune responses, highlighting it as a promising therapeutic target for cancer treatment.

Authors

Hyungsoo Kim, Ze’ev A. Ronai

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Figure 1

Parkin influences tumor immunity through its intrinsic and extrinsic functions.

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Parkin influences tumor immunity through its intrinsic and extrinsic fun...
Parkin is genetically and epigenetically deregulated in cancer. Loss of Parkin results in mitochondrial injury and reduced immune function, including T cell exhaustion. Activity of Parkin E3 ligase within tumor cells after restoration by demethylating therapy alters subcellular trafficking and the release of HMGB1, which activates the GAS/STING pathway. The latter, in turn, activates the IFN pathway, which leads to paracrine activation of CD8+ T cells and innate immune cells, ultimately stimulating antitumor immunity.