RIPK3 binds STUB1

Stable Identifier
R-HSA-9688838
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
RIPK3+ STUB1 => RIPK3:CHIP
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Receptor-interacting serine/threonine protein kinase 3 (RIPK3) functions as a key regulator of necroptosis.The protein stability of RIPK3 is negatively regulated by the C-terminus of HSC70-interacting protein (CHIP, also known as STIP1 homology and U-Box containing protein 1, STUB1) (Seo J et al. 2016). STUB1, as an E3 ligase, mediates ubiquitylation of RIPK3 at Lys55 and Lys363 and targerts it to lysosomal degradation. Coimmunoprecipitation analysis using overexpressed, endogenous or recombinant proteins revealed interactions between STUB1 (CHIP) and RIPK3 in human embryonic kidney 293T (HEK293T) cells (Seo J et al. 2016). Domain mapping revealed that the kinase domain of RIPK3 interacts with the tetratricopeptide repeat (TPR) region of STUB1 (Seo J et al. 2016). Treatment with geldanamycin (an inhibitor of HSP90) induced the degradation of RIPK3 in mouse fibroblasts L929 cells even under STUB1-depleted conditions, suggesting that HSP90 might not be involved in the STUB1-mediated degradation of RIPK3 (Seo J et al. 2016).

Literature References
PubMed ID Title Journal Year
26900751 CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3

Shin, J, Sung, H, Seo, J, Seong, D, Song, J, Kim, JH, Dondelinger, Y, Lee, C, Han, SY, Vandenabeele, P, Lee, EW, Lee, HK, Seong, JK, Jeong, M

Nat. Cell Biol. 2016
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