{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jin X"],"funding":["National Natural Science Foundation of China","Mayo Clinic","NCI NIH HHS"],"pagination":["22-35.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8968458"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["73(1)"],"pubmed_abstract":["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."],"journal":["Molecular cell"],"pubmed_title":["Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression."],"pmcid":["PMC8968458"],"funding_grant_id":["R01 CA207757","R01 CA070292","R01 CA234162","81702374"],"pubmed_authors":["Li H","Jin X","Ma L","Wang B","Ding D","Wu Q","Kohli M","Goodrich DW","Huang H","Yan Y","Ma T","Ye Z","Wang L","Wu H","Rodrigues DN","Dong H","Jimenez R","Zhu R","de Bono J"],"additional_accession":[]},"is_claimable":false,"name":"Phosphorylated RB Promotes Cancer Immunity by Inhibiting NF-κB Activation and PD-L1 Expression.","description":"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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2026-05-30T20:57:14.43Z","creation":"2025-04-04T10:02:03.927Z"},"accession":"S-EPMC8968458","cross_references":{"pubmed":["30527665"],"doi":["10.1016/j.molcel.2018.10.034"]}}