IndraLab

"Thus, the dual role of Rb in regulating cell proliferation and differentiation is mediated by its phosphorylation status. xref Both cyclin D1-CDK4 and cyclin E-CDK2 phosphorylate Rb during the G1/S cell cycle progression, and cyclin D1-CDK4 specifically phosphorylates Rb at Serine 780 in vitro in human fibroblasts. xref We previously reported that sepsis inhibits cyclin-dependent kinase inhibitor p21 expression due to increases in the NFI-A protein. xref P21 inhibits the cyclin D1-CDK4 protein complex, which facilitates cell cycle arrest and promotes cell differentiation. xref , xref In this study, knockdown of cyclin D1 or CDK4 in sepsis Gr1 + CD11b + cells inhibited Rb phosphorylation at Serine 780 ( xref ), Rb knockdown displaced C/EBPβ from the miR promoters and simultaneously induced C/EBPα binding ( xref ) and abolished the miR promoter-driven reporter gene expression ( xref )."

"The cyclin D1-CDK4/6 complex specifically phosphorylates Rb at Ser 780 [ xref ]."

"The RB Ser 807/811 phosphorylation by cyclin E-CDK2 requires RB Ser 780 phosphorylation by cyclin D1-CDK4/6 [ xref ]."

"Conversely, during cell cycle progression, retinoblastoma protein (pRB) is sequentially phosphorylated by CYCLIN-CDK complexes, and CYCLIN D1-CDK4 specifically phosphorylates pRB on the Ser780 residue, leading to its inactivation and the release of E2F. xref In accordance with our transcriptomic data showing that both CCND1 and CDK4 gene expression were downregulated upon TYRO3 depletion (supplementary table  xref ), we observed lower levels of pRB phosphorylation at Ser780 in the three cell lines studied after TYRO3 knockdown, which may, therefore, lead to pRB activation and E2F inactivation, as suggested by IPA analysis of our transcriptomic data (Fig.  xref , lower panel)."

"The active cyclin D1-CDK4 complex phosphorylates the Rb protein at Ser780, which results in the release of the E2F transcription factor from the Rb-E2F complex."