PT  - JOURNAL ARTICLE
AU  - Wang, Yuan
AU  - Wang, Xinting
AU  - Cui, Xiaoteng
AU  - Zhuo, Yue
AU  - Li, Hongshuai
AU  - Ha, Chuanbo
AU  - Xin, Lingbiao
AU  - Ren, Yuanyuan
AU  - Zhang, Wei
AU  - Sun, Xiaoming
AU  - Ge, Lin
AU  - Liu, Xin
AU  - He, Jinyan
AU  - Zhang, Tao
AU  - Zhang, Kai
AU  - Yao, Zhi
AU  - Yang, Xi
AU  - Yang, Jie
TI  - Oncoprotein SND1 hijacks nascent MHC-I heavy chain to ER-associated degradation, leading to impaired CD8<sup>+</sup> T cell response in tumor
AID  - 10.1126/sciadv.aba5412
DP  - 2020 May 01
TA  - Science Advances
PG  - eaba5412
VI  - 6
IP  - 22
4099  - http://advances.sciencemag.org/content/6/22/eaba5412.short
4100  - http://advances.sciencemag.org/content/6/22/eaba5412.full
SO  - Sci Adv2020 May 01; 6
AB  - SND1 is highly expressed in various cancers. Here, we identify oncoprotein SND1 as a previously unidentified endoplasmic reticulum (ER) membrane–associated protein. The amino-terminal peptide of SND1 predominantly associates with SEC61A, which anchors on ER membrane. The SN domain of SND1 catches and guides the nascent synthesized heavy chain (HC) of MHC-I to ER-associated degradation (ERAD), hindering the normal assembly of MHC-I in the ER lumen. In mice model bearing tumors, especially in transgenic OT-I mice, deletion of SND1 promotes the presentation of MHC-I in both B16F10 and MC38 cells, and the infiltration of CD8+ T cells is notably increased in tumor tissue. It was further confirmed that SND1 impaired tumor antigen presentation to cytotoxic CD8+ T cells both in vivo and in vitro. These findings reveal SND1 as a novel ER-associated protein facilitating immune evasion of tumor cells through redirecting HC to ERAD pathway that consequently interrupts antigen presentation.