Reactome | SPOP:CUL3:RBX1 binds to CD274

SPOP:CUL3:RBX1 binds to CD274

Stable Identifier

R-HSA-9929484

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Adaptive Immune System (Homo sapiens)
  - Regulation of T cell activation by CD28 family (Homo sapiens)
    - Co-inhibition by PD-1 (Homo sapiens)
      - Regulation of PD-L1(CD274) expression (Homo sapiens)
        
        Regulation of PD-L1(CD274) Post-translational modification (Homo sapiens)
        
        SPOP-mediated proteasomal degradation of PD-L1(CD274) (Homo sapiens)
        
        SPOP:CUL3:RBX1 binds to CD274 (Homo sapiens)

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The SPOP:CUL3:RBX1 E3 ubiquitin ligase complex regulates the ubiquitination and degradation of PD-L1(CD274) protein. It catalyzes the polyubiquitination of PD-L1 and tags it for the proteasomal degradation. This interaction is negatively regulated by CCND1:CDK4-induced phosphorylation of SPOP and its sequestration by 14-3-3 protein gamma (Zhang et al., 2018, Dong et al., 2022). This binding is also negatively regulated by CK2-mediated phosphorylation of PD-L1 (Zhao et al.,2022).

Literature References

PubMed ID	Title	Journal	Year
36198437	CUL3/SPOP complex prevents immune escape and enhances chemotherapy sensitivity of ovarian cancer cells through degradation of PD-L1 protein Dong, M, Qian, M, Ruan, Z	J Immunother Cancer	2022
29160310	Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance Zhang, J, Bu, X, Wang, H, Zhu, Y, Geng, Y, Nihira, NT, Tan, Y, Ci, Y, Wu, F, Dai, X, Guo, J, Huang, YH, Fan, C, Ren, S, Sun, Y, Freeman, GJ, Sicinski, P, Wei, W	Nature	2018