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Cited by 257

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression

Open access
Jin, Xin, Ding, Donglin, Yan, Yuqian, Li, Hui, Wang, Bo, Ma, Linlin, Ye, Zhenqing, Ma, Tao, Wu, Qiang, Rodrigues, Daniel N., Kohli, Manish, Jimenez, Rafael, Wang, Liguo, Goodrich, David W., de Bono, Johann, Dong, Haidong, Wu, Heshui, Zhu, Runzhi, Huang, Haojie·2019·Molecular Cell
DOI 10.1016/j.molcel.2018.10.034
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Abstract

SUMMARY Aberrant expression of programmed death ligand-1 (PD-L1) in tumor cells promotes cancer progression by suppressing cancer immunity. The retinoblastoma protein RB is a tumor suppressor known to regulate the cell cycle, DNA damage response, and differentiation. Here, we demonstrate that RB interacts with nuclear factor κB (NF-κB) protein p65 and that their interaction is primarily dependent on CDK4/6-mediated serine-249/threonine-252 (S249/T252) phosphorylation of RB. RNA-seq analysis shows a subset of NF-κB pathway genes including PD-L1 are selectively upregulated by RB knockdown or CDK4/6 inhibitor. S249/T252-phosphorylated RB inversely correlates with PD-L1 expression in patient samples. Expression of a RB-derived S249/T252 phosphorylation-mimetic peptide suppresses radiotherapy-induced upregulation of PD-L1 and augments therapeutic efficacy of radiation in vivo. Our findings reveal a previously unrecognized tumor suppressor function of hyperphosphorylated RB in suppressing NF-κB activity and PD-L1 expression and suggest that the RB-NF-κB axis can be exploited to overcome cancer immune evasion triggered by conventional or targeted therapies.

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Metadata

Authors
Jin, X., Ding, D., Yan, Y., Li, H., Wang, B., Ma, L., Ye, Z., Ma, T., Wu, Q., Rodrigues, D. N., Kohli, M., Jimenez, R., Wang, L., Goodrich, D. W., de Bono, J., Dong, H., Wu, H., Zhu, R., & Huang, H.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-01
Volume
73
Issue
1
Pages
22-35.e6
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2018.10.034
OpenAlex
W2901997433
Cited by
257
References
46
FWCI
7.92
Type
journal article
Language
en
Open access
bronze

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The paper
Jin, X., Ding, D., Yan, Y., Li, H., Wang, B., Ma, L., Ye, Z., Ma, T., Wu, Q., Rodrigues, D. N., Kohli, M., Jimenez, R., Wang, L., Goodrich, D. W., de Bono, J., Dong, H., Wu, H., Zhu, R., & Huang, H. (2019). Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.10.034

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.