Fig 2: Pull down assays with the indicated fusion proteins from HEK-293 lysates were performed and binding of B55a was determined by western blot analysis.Two replicates of the experiment showed comparable results.

Fig 3: GST-R1R2 was phosphorylated with Cyclin A/CDK2 where indicated as described in the Manuscript.B55a binding to GST-R1R2 was determined in the presence or absence of OA to prevent dephosphorylation. Proteins were resolved via SDS-PAGE and detected by western blotting using anti-B55a and GST antibodies. Two replicates of the experiment showed comparable results.

Fig 4: BJ-TERT fibroblasts with doxicycline (Dox) inducible WT B55a and B55aD197K stable transgenes where grown to confluency treated with Dox for for 48 h, serum starved for 24 hours and then restimulated with Medium conaning 10% FBS for the indicated times.Expression of indicated proteins and phospho pRB was determined by western blot analysis.

Fig 5: MLH1 loss caused by DNMT3A/B upregulation is mediated through the PP2A-Rb-E2F pathway.a Immunoprecipitation performed with Capturem Protein A columns. Organoid lysates from WT mice were incubated with 1 µg of PPP2R1A antibody for 10 min. The antibody–lysate complex was applied to equilibrate Protein A spin columns. The eluted fraction was then subjected to SDS-PAGE to confirm the presence of PP2A B subunit antigen (52 kDa, detected by Cell Signaling #2290). Images are representative of one biological independent sample for each group. b Volcano plot for the comparison of RNA-seq data of Lgr5-EGFP-CreERT2; Ppp2r1aflox/flox intestinal organoids treated with and without DMBA and tamoxifen for 50 days. Differently expressed genes (fold change >2 and FDR < 0.05) are denoted in red or green. Plot is representative of three biological independent samples for each group. c Intersection of ppp2r1a interaction protein in a and differently expressed genes in b data (IP protein data are available in Supplementary Data 1 and RNA-seq data are available in GSE120241 with NIH/NCBI at GEO dataset). d The top 3 significant gene ontology categories from the 58 interacted proteins identified by GSEA (whole gene ontology category is listed in Supplementary Table 4). e Venn diagram showing overlap (gene numbers) among genes associated with regulation of TP53 activity, cell cycle, and RNA polymerase II transcription. The intersection contained four genes, including hdac2, ppp2cb, akt1, and rb1. Western blot analysis of f CT26 transfected with the indicated shRNAs, and treated with g vehicle control or 5-azacytidine (AZA, 1 µM for 1 days). Blots are representative of three biological independent samples for each group. h Human tissue array containing MSI and MSS colorectal tumours was assayed for p-Rb (n = 141, P = 0.0132) and p-HDAC2 (n = 138, P = 0.02) levels by immunohistochemistry. (Left) Representative pictures showing increased p-Rb and p-HDAC2 levels in MSI compared to MSS. Arrows indicate positive signals. Bar = 25 µm. (Right) Quantitative data are shown. P value was determined by two-sided Mann–Whitney U-test. Source data are provided as a Source data file.