Reactome | PD-L1(CD274) glycosylation and translocation to plasma membrane

PD-L1(CD274) glycosylation and translocation to plasma membrane

Stable Identifier

R-HSA-9931295

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

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)

General

SBML | | PDF

SVG | | PPTX | SBGN

PD-L1(CD274) glycosylation and translocation to plasma membrane

Click the image above or here to open this pathway in the Pathway Browser

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 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). Also, JAK1 activated by IL6 pathway positively regulates the glycosylation process by aiding in the process of recruiting endoplasmic reticulum-associated N-glycosyltransferase STT3A (part of the OST complex) to catalyse PD-L1 glycosylation (Chan et al., 2019). PD-L1 is phosphorylated by IL6-activated JAK1 at Tyr112 (Y112). This process aids in stabilizing the PD-L1 protein. PD-L1, once glycosylated in the ER lumen, get translocated to the Golgi complex for further glycosylation by B3GNT3 (Li et al., 2018) and K63-ubiquitination by MIB2 (Yu et al., 2023). Post Golgi, PD-L1 gets transported to the plasma membrane where it can bind with its receptor and induce immune tolerance.

Literature References

PubMed ID	Title	Journal	Year
36719382	PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination Yu, X, Li, W, Liu, H, Wang, X, Coarfa, C, Cheng, C, Yu, X, Zeng, Z, Cao, Y, Young, KH, Li, Y	J Clin Invest	2023
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
30118680	Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1 Cha, JH, Yang, WH, Xia, W, Wei, Y, Chan, LC, Lim, SO, Li, CW, Kim, T, Chang, SS, Lee, HH, Hsu, JL, Wang, HL, Kuo, CW, Chang, WC, Hadad, S, Purdie, CA, McCoy, AM, Cai, S, Tu, Y, Litton, JK, Mittendorf, EA, Moulder, SL, Symmans, WF, Thompson, AM, Piwnica-Worms, H, Chen, CH, Khoo, KH, Hung, MC	Mol Cell	2018
31305264	IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion Chan, LC, Li, CW, Xia, W, Hsu, JM, Lee, HH, Cha, JH, Wang, HL, Yang, WH, Yen, EY, Chang, WC, Zha, Z, Lim, SO, Lai, YJ, Liu, C, Liu, J, Dong, Q, Yang, Y, Sun, L, Wei, Y, Nie, L, Hsu, JL, Li, H, Ye, Q, Hassan, MM, Amin, HM, Kaseb, AO, Lin, X, Wang, SC, Hung, MC	J Clin Invest	2019
29438695	Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1 Li, CW, Lim, SO, Chung, EM, Kim, YS, Park, AH, Yao, J, Cha, JH, Xia, W, Chan, LC, Kim, T, Chang, SS, Lee, HH, Chou, CK, Liu, YL, Yeh, HC, Perillo, EP, Dunn, AK, Kuo, CW, Khoo, KH, Hsu, JL, Wu, Y, Hsu, JM, Yamaguchi, H, Huang, TH, Sahin, AA, Hortobagyi, GN, Yoo, SS, Hung, MC	Cancer Cell	2018