Reactome | CD274 N-linked glycosylation in ER

CD274 N-linked glycosylation in ER

Stable Identifier

R-HSA-9931286

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

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)
        
        PD-L1(CD274) glycosylation and translocation to plasma membrane (Homo sapiens)
        
        CD274 N-linked glycosylation in ER (Homo sapiens)

General

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PD-L1 (CD274) glycosylation plays a critical role in determining the protein function and stability. PD-L1 is N-glycosylated at N192, N200 and N219 by the OST complex (STT3A and STT3A) in the ER lumen. This process is important for PD-L1 stability and inhibits its targeting for proteasomal degradation by GSK3B (Li et al., 2016, Hsu et al., 2018). Also, JAK1 activated by the IL6 pathway positively regulate the glycosylation process by aiding in the recruitment of endoplasmic reticulum-associated N-glycosyltransferase STT3A (part of the OST-A complex) to catalyse PD-L1 glycosylation (Chan et al., 2019).

Literature References

PubMed ID	Title	Journal	Year
27572267	Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity Li, CW, Lim, SO, Xia, W, Lee, HH, Chan, LC, Kuo, CW, Khoo, KH, Chang, SS, Cha, JH, Kim, T, Hsu, JL, Wu, Y, Hsu, JM, Yamaguchi, H, Ding, Q, Wang, Y, Yao, J, Lee, CC, Wu, HJ, Sahin, AA, Allison, JP, Yu, D, Hortobagyi, GN, Hung, MC	Nat Commun	2016
29765039	STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion Hsu, JM, Xia, W, Hsu, YH, Chan, LC, Yu, WH, Cha, JH, Chen, CT, Liao, HW, Kuo, CW, Khoo, KH, Hsu, JL, Li, CW, Lim, SO, Chang, SS, Chen, YC, Ren, GX, Hung, MC	Nat Commun	2018