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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.
Pubmed ID: 30527665 RIS Download
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View all literature mentionsThis polyclonal secondary targets IgG, Light Chain Specific
View all literature mentionsThis monoclonal targets NF-κB1
View all literature mentionsThis monoclonal targets NF-κB p65
View all literature mentionsThis polyclonal targets PD-L1/CD274
View all literature mentionsThis monoclonal targets CHD-1
View all literature mentionsThis monoclonal targets Cleaved Caspase-3 (Asp175) (D3E9) Rabbit mAb
View all literature mentionsThis monoclonal targets c-Rel (B-6)
View all literature mentionsThis monoclonal targets TAK1 (D94D7) Rabbit mAb
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis monoclonal targets Phospho-Rb (Ser249, Thr252)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Human IKBKB
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets RelB (D-4)
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis polyclonal targets Cdk6 (C-21)
View all literature mentionsThis polyclonal targets Phospho-Rb (Ser795)
View all literature mentionsThis monoclonal secondary targets IgG, Light Chain Specific
View all literature mentionsThis monoclonal targets MAPK1
View all literature mentionsThis monoclonal targets CHUK
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis monoclonal targets Retinoblastoma Protein
View all literature mentionsThis monoclonal targets NFKB2
View all literature mentionsThis polyclonal targets Phospho-NF-kappaB p65 (Ser536)
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets PD-L1
View all literature mentionsThis monoclonal targets Ly-6G Ly-6C
View all literature mentionsThis monoclonal targets beta-Tubulin
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis polyclonal targets PD-L1/CD274
View all literature mentionsThis monoclonal targets Retinoblastoma Protein
View all literature mentionsThis monoclonal targets Phospho-Rb (Ser249, Thr252)
View all literature mentionsThis monoclonal targets NF-κB1
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets PD-L1
View all literature mentionsThis monoclonal targets NF-κB p65
View all literature mentionsThis monoclonal targets NFKB2
View all literature mentionsThis monoclonal targets c-Rel (B-6)
View all literature mentionsThis polyclonal targets Phospho-Rb (Ser795)
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets Ly-6G Ly-6C
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis polyclonal secondary targets IgG, Light Chain Specific
View all literature mentionsThis monoclonal secondary targets IgG, Light Chain Specific
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis monoclonal targets MAPK1
View all literature mentionsThis monoclonal targets beta-Tubulin
View all literature mentionsThis monoclonal targets Human IKBKB
View all literature mentionsThis monoclonal targets CHUK
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis polyclonal targets Phospho-NF-kappaB p65 (Ser536)
View all literature mentionsThis monoclonal targets Cleaved Caspase-3 (Asp175) (D3E9) Rabbit mAb
View all literature mentionsThis monoclonal targets CHD-1
View all literature mentionsThis monoclonal targets TAK1 (D94D7) Rabbit mAb
View all literature mentionsThis monoclonal targets RelB (D-4)
View all literature mentionsThis polyclonal targets Cdk6 (C-21)
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