Reactome | RIPK3 binds STUB1

RIPK3 binds STUB1

Stable Identifier

R-HSA-9688838

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

Synonyms

RIPK3+ STUB1 => RIPK3:CHIP

ReviewStatus

5/5

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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 proteins revealed interactions between STUB1 (CHIP) and RIPK1 in human embryonic kidney 293T (HEK293T) cells (Seo J et al. 2016). Interactions of endogenous STUB1 and RIPK1 proteins was detected in mouse fibroblast L929 cells. Direct interaction between recombinant proteins was confirmed by GST-pull-down assay (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 Seo, J, Lee, EW, Sung, H, Seong, D, Dondelinger, Y, Shin, J, Jeong, M, Lee, HK, Kim, JH, Han, SY, Lee, C, Seong, JK, Vandenabeele, P, Song, J	Nat. Cell Biol.	2016