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Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance
Open accessAbstract
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, and the underlying mechanism(s) is not well understood. Recent studies revealed that response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumour cells. Hence, it is important to understand the mechanistic pathways that control PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1-PD-L1 blockade in patients with cancer. Here we show that PD-L1 protein abundance is regulated by cyclin D-CDK4 and the cullin 3-SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of speckle-type POZ protein (SPOP) and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1. Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumour-infiltrating lymphocytes in mouse tumours and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD-1 immunotherapy enhances tumour regression and markedly improves overall survival rates in mouse tumour models. Our study uncovers a novel molecular mechanism for regulating PD-L1 protein stability by a cell cycle kinase and reveals the potential for using combination treatment with CDK4/6 inhibitors and PD-1-PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers.
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“Moreover, several critical proteins including CMTM4, CMTM6, GSK3β, CSN5, CDK4, CDK6, and palmitoylated B3GNT3 have been shown to affect post-translational PD-L1 stability31–36.”
From PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells (2022) · cites this paper as [36]
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“the Cullin 3-SPOP E3-ligase complex can directly ubiquitinate PD-L1 in a cell-cycle dependent manner, leading to its degradation [15].”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [15]
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“First, as previously described [15], perturbation of the CUL3-SPOP complex interferes with the ubiquitination of PD-L1, directly enhancing its stability and protein expression level.”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [15]
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“we verified that perturbation of BHLH transcription factor MYC [12] and the ubiquitin ligase CUL3 [15] both increased PD-L1 protein levels, consistent with previous reports.”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [15]
In the citing paper
“CDK4 was shown to have kinase activity towards SPOP, a cullin 3 E3 ubiquitin ligase adaptor protein that can interact with PD-L1 (Zhang et al., 2018).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Zhang et al., 2018
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“Treatment with palbociclib inhibits SPOP phosphorylation, promoting its degradation and blocking PD-L1 proteasome mediated degradation.”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Zhang et al., 2018
In the citing paper
“Combining palbociclib with a PD-1 blockade enhanced tumor regression and improved overall survival in mouse xenograft models of colon adenocarcinoma (Deng et al., 2017; Zhang et al., 2018).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Zhang et al., 2018
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878
Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,261
The Molecular Taxonomy of Primary Prostate Cancer
Abeshouse, A. A., Ahn, J., Akbani, R., Ally, A., Amin, S. B., Andry, C., Annala, M., Aprikian, A. G., Armenia, J., Arora, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.025 · Cited by 3,126
Zou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,400
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990
Self-citationTaxol stabilizes microtubules in mouse fibroblast cells.
Schiff, P. B., & Horwitz, S. B. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.3.1561 · Cited by 1,971
Cell cycle proteins as promising targets in cancer therapy
Otto, T., & Siciński, P. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.138 · Cited by 1,931
Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
Barbieri, C. E., Baca, S. C., Lawrence, M. S., Demichelis, F., Blattner, M., Theurillat, J.-P. P., White, T. A., Stojanov, P., Allen, E. M. V., Stransky, N., et al. (2012) · Nature Genetics · doi:10.1038/ng.2279 · Cited by 1,550
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Items 701–800 of 1,000
Vučinić, D., Grahovac, M., Grahovac, B., Mohar, B., Kovač, L., Belušić-Gobić, M., & Zamolo, G. (2021) · Pathology - Research and Practice · doi:10.1016/j.prp.2021.153725 · Cited by 6
Feng, D., Tuo, Z., Wang, J., Ye, L., Li, D., Wu, R., Wei, W., Yang, Y., & Zhang, C. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e23495 · Cited by 7
Self-citationThe role of the master cancer regulator Pin1 in the development and treatment of cancer
Stewart, R., Sharma, S., Wu, T., Okuda, S., Xie, G., Zhou, X. Z., Shilton, B. H., & Lu, K. P. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1343938 · Cited by 7
Synergistic Enhancement of Antitumor Effects by Combining Abemaciclib with Desipramine
Li, Y., Sung, Y., Choi, Y. E., Choi, Y., & Goh, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137407 · Cited by 6
Research progress on gene mutations and drug resistance in leukemia
Ma, X., Xu, J., Wang, Y., Fleishman, J. S., Bing, H., Yu, B., Li, Y., Bo, L., Zhang, S., Chen, Z., et al. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101195 · Cited by 7
Chemotherapy‐Mediated Induction of PD‐L1 via SEI1 Facilitates Myeloma Immune Evasion
Chen, R., Li, Z., Fang, Z., Li, Z., Yang, D., Li, Y., Liu, S., Liu, Z., Liu, R., & Liu, H. (2025) · Advanced Science · doi:10.1002/advs.202411082 · Cited by 6
TBB inhibits CK2/PD-L1/EGFR pathway-mediated tumor progression
Che, S., Zhang, Y., Xu, H., Shi, J., & Hou, Y. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177689 · Cited by 7
Zhou, C., Lian, Y., Cheng, J., Liu, H., Du, G., & Shi, J. (2025) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2025.138203 · Cited by 6
Bugia, L., Affolter, A., Kern, J., Sohn, E., Jungbauer, F., Fleckenstein, J., Lammert, A., Rotter, N., & Scherl, C. (2025) · Oncology Reports · doi:10.3892/or.2025.8984 · Cited by 6
Tumor PD-L1 induces β2m ubiquitylation and degradation for cancer cell immune evasion
Zhao, Q., Li, C., Zhang, M., Gao, T., Wang, Z., Li, Z., Qin, Y., Xue, X., Chen, M., Xu, C., et al. (2026) · Cell Research · doi:10.1038/s41422-025-01205-5 · Cited by 7
Strategies to target PD-1/PD-L1 in the tumor microenvironment
Kui, Y., Tong, F., Zhang, R., Dong, X., & Wang, J. (2026) · Cellular Oncology · doi:10.1007/s13402-026-01181-x · Cited by 8
Hu, X., Wang, M., Shi, S., Raja, M. R. K., Gupta, G., Chen, H., & Xu, P. (2023) · Biomaterials Science · doi:10.1039/d3bm00627a · Cited by 6
SPOP promotes CREB5 ubiquitination to inhibit MET signaling in liver cancer
Gong, D.-A., Zhou, P., Chang, W.-Y., Yang, J.-Y., Zhang, Y.-L., Huang, A., Tang, N., & Wang, K. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2023.119642 · Cited by 6
Targeting CENP-E augments immunotherapy in non-small cell lung cancer via stabilizing PD-L1
Liang, J., Tian, C., Liu, L., Zeng, X., & Zhang, Y. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111294 · Cited by 6
Anti-Tumor Potential of Post-Translational Modifications of PD-1
Xi, X., & Zhao, W. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46030136 · Cited by 6
Recent Developments in Targeting the Cell Cycle in Melanoma
Hung, C., Nguyen, T. T. T., Poulikakos, P. I., & Polsky, D. (2025) · Cancers · doi:10.3390/cancers17081291 · Cited by 7
See, K., Kadonosono, T., Miyamoto, K., tsubaki, T., Ota, Y., Katsumi, M., Ryo, S., Aida, K., Minegishi, M., Isozaki, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-01603-w · Cited by 6
Biomarkers for therapy selection in metastatic urothelial cancer
Jun, T. W., Anker, J. F., & Galsky, M. D. (2022) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2021.171 · Cited by 8
Cui, C., Wu, Q., Zhou, H., He, H., Wang, Y., Tang, Z., Zhang, Y., Wang, X., Xiao, J., & Zhang, H. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-5783 · Cited by 5
Jeong, J. H., Park, S., Lee, S. Y., Kim, Y., Shim, I. K., Jeong, S.-Y., Choi, E. K., Kim, J., & Jun, E. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110451 · Cited by 6
Zaemes, J. P., Alzeer, A., Villa, K., & Atkins, M. B. (2020) · Immunotherapy · doi:10.2217/imt-2020-0139 · Cited by 6
Sorting nexin 6 interacts with Cullin3 and regulates programmed death ligand 1 expression
Ghosh, C., Xing, Y., Li, S., Hoyle, R. G., Sun, M., Li, J., & Sun, Y. (2021) · FEBS Letters · doi:10.1002/1873-3468.14191 · Cited by 6
Self-citationQuiescence and aging of melanocyte stem cells and a novel association with programmed death-ligand 1
Palmer, J. W., Villavicencio, K. M., Idris, M. I., Baranyk, I. J., Polycarp, N., Dawson, A. D., Weddle, D., Pavan, W. J., Filipp, F. V., & Harris, M. L. (2024) · iScience · doi:10.1016/j.isci.2024.110908 · Cited by 6
Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors
Kim, U., McCormick, T. S., Mangla, A., Cooper, K. D., Schwartz, G. K., & Yoshida, A. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107955 · Cited by 6
SPOP and MMR/MSI alterations in prostate cancer: relationship with PD-L1, TILs and AR expression
Fiorentino, V., Germanà, E., Ricciardi, G., Capodimonti, S., Cenci, T., Orlandi, A., Zuccalà, V., Guida, E., Ficarra, V., Pizzimenti, C., et al. (2025) · Pathologica · doi:10.32074/1591-951x-n979 · Cited by 5
Spop-binding bifunctional degraders: a novel approach for cancer immunotherapy
Cheng, B., Kong, Z., Shi, Y., Wu, Y., Du, J., Wang, S., Chen, J., & Wen, C. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.11.042 · Cited by 5
Ageta, H., Shimada, Y., Nagaoka, T., Takenaka, K., Yoshioka, Y., Konno, K., Amemiya, R., Nagase, K., Hitachi, K., Onouchi, T., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-27789-x · Cited by 5
CDK10 suppresses nucleic acid sensors-mediated antitumor immunity
Xu, G., Guo, F., He, C., Wang, X., Xiang, B., Fan, L., Chen, B., Peng, J., Sun, Y., Shi, J., et al. (2026) · Nature Cancer · doi:10.1038/s43018-025-01100-3 · Cited by 5
Self-citationThe Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases
Liang, X.-B., Dai, Z.-C., Zou, R., Tang, J., & Yao, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713558 · Cited by 5
Wang, M., Guo, H., Sun, B.-B., Jie, X., Shi, X., Liu, Y., Shi, X.-L., Ding, L., Xue, P.-H., Qiu, F., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155825 · Cited by 5
CDK4/6 Inhibitor Resistance in ER+ Breast Cancer
Migliaccio, I., Guarducci, C., & Malorni, L. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-70875-6_23 · Cited by 5
Proteasomal Dysfunction in Cancer: Mechanistic Pathways and Targeted Therapies
Bagde, P. H., Kandpal, M., Rani, A., Kumar, S., Mishra, A., & Jha, H. C. (2025) · Journal of Cellular Biochemistry · doi:10.1002/jcb.70000 · Cited by 6
Tang, L., Hu, Y., Wang, C., Han, W., & Wang, P. (2025) · FEBS Journal · doi:10.1111/febs.70089 · Cited by 5
O’Farrell, J., Lapp, C., Kuznia, H., & Afzal, M. Z. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14124322 · Cited by 5
Shi, J., Dong, X., Han, W., Zhou, P., Liu, L., Wang, H., Jiang, Q., Li, H., Cheng, S., Li, S., et al. (2021) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000001217 · Cited by 5
Self-citationICSBP-induced PD-L1 enhances osteosarcoma cell growth
Sung, J. Y., Kim, J. H., Kang, H. G., Park, J. W., Park, S.-Y., Park, B.-K., & Kim, Y.-N. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.918216 · Cited by 5
Byeon, H.-E., Haam, S., Han, J. H., Lee, H. W., & Koh, Y. W. (2022) · Cancers · doi:10.3390/cancers15010197 · Cited by 5
Advances in research on potential inhibitors of multiple myeloma
Tang, G., Huang, S., Luo, J., Wu, Y., Zheng, S., Tong, R., Zhong, L., & Shi, J. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115875 · Cited by 5
Zhang, Y., Zhang, N., Song, W., Yousuf, S., & Li, W. (2023) · Journal of Cancer · doi:10.7150/jca.84652 · Cited by 5
Gan, S., Qu, F., Zhang, X., Pan, X., Xu, D., Cui, X., & Hou, J. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113857 · Cited by 5
Pharmacological inhibition of neddylation impairs long interspersed element 1 retrotransposition
Li, Y., Shen, S., Guo, H., Li, H., Zhang, L., Zhang, B., Yu, X.-F., & Wei, W. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113749 · Cited by 5
Self-citationBrandariz, J., de Llobet, L., Esquefa, V., Aguilar, D., Salca, A., Arce-Gallego, S., Cresta Morgado, P., Sole, A., Agundez, L., Mir, G., et al. (2025) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0903 · Cited by 5
Inhibition of Skp2 enhances anti-tumor immunity of macrophages by regulating CD47 in gastric cancer
Hu, K., Zhao, L., Miao, P., Qiu, W., Ai, L., Chen, X., Wang, S., Chen, X., & Shi, X. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115262 · Cited by 5
Cheng, F., Zeng, C., Zeng, L., Wu, C., & Chen, Y. (2019) · Medicine · doi:10.1097/md.0000000000017439 · Cited by 5
Kinase inhibitors: Opportunities for small molecule anticancer immunotherapies
Safaroghli‐Azar, A., Emadi, F., Lenjisa, J. L., Mekonnen, L. B., & Wang, S. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103525 · Cited by 5
Xia, H., Wang, M., Jiang, X., Wu, F., Xu, H., Lin, Z., & Qi, B. (2018) · Glioma · doi:10.4103/glioma.glioma_10_18 · Cited by 5
Self-citationProspects of the potential strategies to improve the efficacy of anti‐PD‐1/PD‐L1 therapy
Yamaguchi, H., Wang, S., & Hung, M. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.803 · Cited by 4
p16-dependent upregulation of PD-L1 impairs immunosurveillance of senescent cellsPreprint
Majewska, J., Agrawal, A., Mayo, A., Roitman, L., Chatterjee, R., Kralova, J. S., Landsberger, T., Katzenelenbogen, Y., Meir-Salame, T., Hagai, E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.30.524522 · Cited by 5
Tang, J., Liu, H., Li, J., Zhang, Y., Yao, S., Yang, K., You, Z., Qiao, X., & Song, Y. (2024) · Future Medicinal Chemistry · doi:10.1080/17568919.2024.2366146 · Cited by 5
Proteostasis of immune checkpoint receptors
Tey, P. Y., Urbé, S., & Clague, M. J. (2025) · Biochemical Journal · doi:10.1042/bcj20253299 · Cited by 4
Minati, R., Cahuzac, M., Perrault, J., Lullier, V., Apavaloaei, A., Bonneil, É., Courcelles, M., Lanoix, J., Kina, E., Perreault, C., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116676 · Cited by 4
The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity
Si, Y., Li, H., & Shi, Y. (2025) · Cancers · doi:10.3390/cancers17243997 · Cited by 4
Yan, P., Bu, X., Hou, T., Chen, L., Zhong, G., Huang, D., Wang, J., Qi, Y., Jiang, W., Li, Z., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-013498 · Cited by 4
Self-citationLi, S., Gong, Y., Li, H., Liu, S., Yin, Y., Yu, Y., Chu, Y., Hou, J., Liu, J., Zhang, H., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03786-w · Cited by 4
Nasr, S., Li, L., Asad, M., Moridi, M., Wang, M., Zemp, F. J., Mahoney, D. J., & Wang, E. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105167 · Cited by 4
Sinha, D., Moseley, P., Lu, X., Wright, Q., Gabrielli, B. G., Frazer, I. H., & Cruz, J. L. G. (2022) · Cancers · doi:10.3390/cancers14246150 · Cited by 4
Wang, J., Luo, L., Liang, D., Guo, C., Huang, Z., Jian, X., & Wen, J. (2023) · World Journal of Clinical Cases · doi:10.12998/wjcc.v11.i23.5416 · Cited by 4
Kobayashi, T., Nishimura, M., Hosonaga, M., Kizawa, R., Kawai, S., Aoyama, Y., Ozaki, Y., Fukada, I., Hara, F., Takano, T., et al. (2024) · BMC Cancer · doi:10.1186/s12885-024-12941-z · Cited by 4
Biochemical analysis of PD-L1 ubiquitination by CRL3SPOP, ARIH1, and NEDD4 family ubiquitin ligases
Xie, G., Gao, L., Lu, R., Tian, L., Zheng, T., Li, X., Dang, Y., Cole, P. A., Yu, X., Jiang, H., et al. (2025) · Structure · doi:10.1016/j.str.2025.05.005 · Cited by 4
CDK4/6 inhibition protects normal cells against cancer therapy-induced damage
Boopathi, E., & Thangavel, C. (2020) · Translational Cancer Research · doi:10.21037/tcr.2019.12.86 · Cited by 4
Phosphorylation: A Fast Switch For Checkpoint Signaling
Wang, Y., Wang, P., & Xu, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3266-5_15 · Cited by 4
Immunogenomic profiles associated with response to life-prolonging agents in prostate cancer
Conteduca, V., Brighi, N., Schepisi, G., & Giorgi, U. D. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02354-3 · Cited by 4
Deng, L., Zhou, J., Sun, Y. L., Hu, Y., Qiao, J., Liu, Z., Gu, L., Lin, D., Zhang, L., & Deng, D. (2024) · Gastric Cancer · doi:10.1007/s10120-024-01515-4 · Cited by 4
Self-citationWang, J., Zhuang, H., Zhang, H., Li, Q., Cao, X., Lin, Z.-H., Lin, T., Chen, X., Ni, X., Yang, J., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.04.002 · Cited by 4
Self-citationSPOP Inhibition of Endometrial Carcinoma and Its Clinicopathological Relationship
Zhu, Q., Zhang, G., Tang, M., Zheng, R., & Gan, H. (2022) · Applied Bionics and Biomechanics · doi:10.1155/2022/5721630 · Cited by 4
RetractedDecoding Heterogenous Single-cell Perturbation ResponsesPreprint
Song, B., Liu, D., Dai, W., McMyn, N. F., Wang, Q., Yang, D., Krejčí, A., Vasilyev, A., Untermoser, N., Loregger, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.30.564796 · Cited by 4
Chen, Y., Liu, W., Cai, Q., Pan, C., Yin, Z., Tang, Y., He, Z., Cheng, G., & Shu, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1570040 · Cited by 3
Xu, H., Wang, Y., Sa, Q., Zhou, Y., Ma, F., Zhang, P., Fan, Y., Cai, R., Li, Q., Lan, B., et al. (2025) · The Breast · doi:10.1016/j.breast.2025.104598 · Cited by 3
Druggable genome CRISPR screening identifies the KEAP1/NRF2 axis as a mediator of PD-L1 expression
Seker-Polat, F., Rogozinska, M., Ban, Y. H., Abdula, F., Buyukcelebi, K., Xie, P., Fan, J., Abbaszadeh, N., Kingham, Y., Paylakhi, S. Z., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08983-z · Cited by 3
Pan, Y., Zeng, C., He, Y. L., Chang, R., Wu, J., Yuan, C., Li, H., Su, C., Han, M., Li, P., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-68156-8 · Cited by 3
Safaroghli‐Azar, A., Mekonnen, L. B., Lenjisa, J. L., Milne, R. W., & Wang, S. (2026) · Journal of Hematology & Oncology · doi:10.1186/s13045-026-01794-7 · Cited by 5
Claaß, L. V., Schultheiß, C., Scholz, R., Paschold, L., Simnica, D., Heinemann, V., Stintzing, S., & Binder, M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.941666 · Cited by 3
Cui, Y. J., Zhao, Y., Shen, G., Lv, Q., & Ma, L. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102038 · Cited by 3
Jia, Y., Liu, M., Liu, H., Liang, W., Zhu, Q., Wang, C., Chen, Y., Gao, Y., Liu, Z., & Cheng, X. (2024) · Cancer Biology & Therapy · doi:10.1080/15384047.2024.2425134 · Cited by 3
Yao, Y., Hong, S., Yoshida, S., Swaroop, V., Curtin, B., & Inoki, K. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115101 · Cited by 3
Cul3 substrate adaptor SPOP targets Nup153 for degradation
Ong, J. Y., Abdusamad, M., Ramírez, I., Gholkar, A. A., Zhang, X., Gimeno, T. V., & Torres, J. Z. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-04-0198 · Cited by 3
Proteasome Inhibition Induces IRF1 Downstream Molecules Independently of JAK Activity in Cancers
Takahashi, K., Takahashi, A., Takahashi, N., Zhou, Y., Sakurai, H., & Yokoyama, S. (2025) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b25-00006 · Cited by 3
Xiao, Y., Li, G., Xie, Y., Shao, B., Hao, J., Zhu, Y.-L., Kong, D., Qin, Y., Qin, H., Ren, S., et al. (2025) · PeerJ · doi:10.7717/peerj.19550 · Cited by 3
Self-citationZhang, Y., Sun, B., Zhou, R., Gong, Z., Han, Y., Tao, W., Shi, C., Zhang, W., Liu, L., Zhang, Z., et al. (2025) · Advanced Science · doi:10.1002/advs.202510501 · Cited by 3
He, Y., Chen, J., Peng, X., Xia, Y., & Su, Y. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02329-5 · Cited by 3
Molecular profiles of different PD-L1 expression in patients with esophageal squamous cell carcinoma
Zhao, S., Hu, X., Zhou, P., Li, A., Chen, L., Wang, D., He, J., & Jiang, Y. (2023) · Cancer Biology & Therapy · doi:10.1080/15384047.2023.2256927 · Cited by 3
SPOP inhibits HBV transcription and replication by ubiquitination and degradation of HNF1α
Pi, Y., Li, Y., Yan, Q., Luo, H., Zhou, P., Chang, W.-Y., Gong, D.-A., Hu, Y., Wang, K., Tang, N., et al. (2023) · Journal of Medical Virology · doi:10.1002/jmv.29254 · Cited by 3
Isobutyric Acid Promotes Immune Evasion in Colorectal Cancer via Increased PD ‐ L1 Expression
Lin, Q., Wang, H., Chen, W., Wei, X., Chen, J., Deng, Y., Wei, C., Lai, H., Mo, X., Tang, W., et al. (2024) · Cancer Medicine · doi:10.1002/cam4.70397 · Cited by 3
Self-citationUbiquitination of Immune System and Cancer Therapy
Du, Y., Zhang, H., & Hu, H. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-981-97-7288-9_3 · Cited by 3
Feng, Z., Qin, M., Jiang, J., Wang, M., Zhang, T., Li, Y., Liu, X., Zhang, J., Shi, H., Zhao, Y., et al. (2025) · Nano Letters · doi:10.1021/acs.nanolett.4c06018 · Cited by 3
Self-citationSplit Cyclin-Dependent Kinase 4/6–Retinoblastoma 1 Axis in Pancreatic Cancer
Huang, X., & Zhang, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602352 · Cited by 3
The clinical and prognostic significance of CMTM6/PD-L1 in oncology
Yaseen, M. M., Abuharfeil, N. M., & Darmani, H. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-022-02811-0 · Cited by 2
Different Cyclins and Their Significance in Breast Cancer
Mir, M. A., & Qayoom, H. (2023) · Springer eBooks · doi:10.1007/978-981-19-8911-7_17 · Cited by 3
CDK1/2/5 blockade: killing two birds with one stone
Liu, J., Kang, R., & Tang, D. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1875612 · Cited by 3
Ke, S., Dang, F., Wang, L., Chen, J.-Y., Naik, M., Thavamani, A., Liu, Y.-S., Li, W.-X., Kim, N., Naik, N., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2447544/v1 · Cited by 2
Chen, X., Li, S., Cao, L., Chen, S., Lin, Q., & Zhong, S. (2025) · Discover Oncology · doi:10.1007/s12672-025-01768-0 · Cited by 2
Kim, D., Park, J., Kim, Y., Na, O., Park, M., Zhang, S., Cho, S., & Chung, Y. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03675-4 · Cited by 2
Chen, X., Qin, Y., Gan, J., Wei, T., Wei, X., Xiong, Y., Zhang, Z., & Wei, B. (2025) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2025.2483558 · Cited by 2
SMARCD1 is a dual regulator of PD-L1 expression and cell proliferation facilitating tumor evasion
Fu, G., Liu, Y., Chen, Q., Yang, Z., Luo, M., & Cai, W. X. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.155975 · Cited by 2
Li, Y., Qu, L., Tang, Y., Ni, F., Shen, S., Guo, H., Yu, X., & Wei, W. (2025) · Journal of Virology · doi:10.1128/jvi.00354-25 · Cited by 2
Self-citationHe, S., Zhao, S., Luo, X., Liu, N., Zhang, Y., Wang, S., Yang, Y., Ma, L., & Zhang, C. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.147361 · Cited by 2
Zhu, J., Zhang, L., Hui, X., Shang, L., Ma, J., & Zhang, Q. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115580 · Cited by 2
Modulation of the tumor microenvironment by the ubiquitin–proteasome system in colorectal cancer
Wang, X., Ren, Y., Song, R., Liu, J., Zhou, Y., Yang, S., Liu, Y., Lei, Y., & Zhao, X. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07487-y · Cited by 3
Zhou, Z., Lu, Y., Li, P., Liu, X., Cheng, W., Chen, H.-N., Dai, L., & Ren, H. (2026) · PLoS Biology · doi:10.1371/journal.pbio.3003603 · Cited by 2
Dey, D. K., Ganguly, K., Kujur, E., & Basak, S. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218314 · Cited by 2
Metadata
- Authors
- Zhang, J., Bu, X., Wang, H., Zhu, Y., Geng, Y., Nihira, N. T., Tan, Y., Ci, Y., Wu, F., Dai, X., Guo, J., Huang, Y.-H., Fan, C., Ren, S., Sun, Y., Freeman, G. J., Sicinski, P., & Wei, W.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Second Military Medical University (CN)
- Corresponding author
- Freeman, Gordon J.
- Wei, Wenyi
- ORCID
- Venue
- Nature
- Published
- 2017-11-16
- Volume
- 553
- Issue
- 7686
- Pages
- 91-95
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5754234
- OpenAlex
- W2769376007
- Cited by
- 1,013
- References
- 43
- Citations by year
- 2026: 81 · 2025: 123 · 2024: 138 · 2023: 140 · 2022: 134 · 2021: 157 · 2020: 118 · 2019: 78 · 2018: 43
- FWCI
- 28.82
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-07-03)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Cancer Institute (R01CA190509, R01CA229307, R01CA200573, K99CA212292, R01CA177910, P50CA101942, R01CA132740, R01CA202634, P01CA080111, R01CA200651, R01CA083688)
- National Institute of General Medical Sciences (R01GM094777, R01GM089763)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PD-L1, anti-PD-1 therapy, CDK4/6 inhibitors, FZR1, proteasomal degradation, polyubiquitination, tumor immune evasion, immune checkpoint blockade, combination immunotherapy, tumor immune microenvironment
- MeSH terms
- Animals, Cell Cycle, Cell Line, Female, Humans, Immunologic Surveillance, Male, Neoplasms, Nuclear Proteins, Phosphorylation, Prostatic Neoplasms, Repressor Proteins, Lymphocytes, Tumor-Infiltrating, Tumor Escape, Cullin Proteins, Proteasome Endopeptidase Complex, 14-3-3 Proteins, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Mice, Protein Stability, Cyclin D, Proteolysis, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Cdh1 Proteins
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