- [Resource Hub](/) - [Publication](/?resource-type=publication#library) - Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry # Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry Ke S, Dang F, Wang L, Chen JY, Naik MT, Li W, et al. Nature Communications . 2024;15(1):3220. DOI [10.1038/s41467-024-47427-w](https://doi.org/10.1038/s41467-024-47427-w). PMID 38622115. PMCID PMC11018817. How to cite ### AMA Ke S, Dang F, Wang L, Chen JY, Naik MT, Li W, et al. Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry. Nat Commun . 2024;15(1):3220. doi:10.1038/s41467-024-47427-w ### APA Ke, S., Dang, F., Wang, L., Chen, J.-Y., Naik, M. T., Li, W., et al. (2024). Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry. Nature Communications , 15(1), 3220. https://doi.org/10.1038/s41467-024-47427-w ### BibTeX @article{ke2024reciprocal, title = {Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry}, author = {Ke, S. and Dang, F. and Wang, L. and Chen, J.-Y. and Naik, M. T. and Li, W. and others}, journal = {Nature Communications}, volume = {15}, number = {1}, pages = {3220}, year = {2024}, doi = {10.1038/s41467-024-47427-w}, pmid = {38622115} } Whether a cell commits to divide comes down to which regulatory proteins are held steady and which are marked for destruction. Two opposing enzymes sit at the center of that decision, and when their balance tips, cells push into the cycle when they should stay quiet — a pattern common in aggressive breast cancer. This study maps a reciprocal antagonism between the prolyl isomerase PIN1 and the APC/C-CDH1 degradation complex, where each one restrains the other to keep mitotic proteins at the level a normal cycle needs. In triple-negative breast tumors, PIN1 ran high inside the tumor cells themselves and was tied to patient follow-up, and blocking PIN1 together with a CDK4/6 inhibitor forced cells out of the cycle and slowed tumor growth more than either drug alone. [Read publication at Nature Communications](https://pmc.ncbi.nlm.nih.gov/articles/PMC11018817/) ## Key findings - PIN1 and the APC/C-CDH1 ubiquitin ligase hold each other in check. PIN1's enzymatic activity flips a target proline into its active shape; here that isomerization roughly doubled the cis form of the peptide, from 7% to 14.2%, the switch that sets how long mitotic proteins survive. - Blocking PIN1 and CDK4/6 together outperformed either drug alone in triple-negative breast cancer. In mouse models, the PIN1 inhibitor Sulfopin (40 mg/kg) plus the CDK4/6 inhibitor Palbociclib (100 mg/kg) delayed tumor progression and extended overall survival beyond either monotherapy. - In breast tumor microarrays, PIN1 was read specifically inside the tumor cells. Quantified in the tumor (PanCK+) compartment, samples were split into PIN1-high versus PIN1-low at an upper-tertile threshold (score ≥2), tying a tumor-cell-specific PIN1 level to each sample's clinical follow-up. ## CyteFinder in the methods “Breast tissue microarrays (TMAs) (BrCaStg1) were acquired from Cooperative Human Tissue Network’s Mid-Atlantic Division. Each TMA underwent a dual staining process using panCK (Invitrogen 41-9003-82) and PIN1 (Abcam, ab192036) per manufacturer’s recommendations. Image capture was executed using the CyteFinder high-throughput imaging system (RareCyte WA). We saved 10x magnification images from each TMA-slide in a 3-channel (DAPI/ Cy3/Cy5) configuration as Bio-format stacks.” — Ke et al., Nature Communications (2024), Methods, “Tissue microarray staining, image acquisition and analysis” ## Why it matters for CyteFinder users If you are weighing CyteFinder for tissue work, look at the step it carried here. The team needed to read one protein — PIN1 — not across a whole tumor section, but specifically inside the tumor cells, separated from the surrounding stroma. That is a compartment problem, and it is why they imaged the breast tissue microarrays on CyteFinder in three fluorescence channels (DAPI, PanCK, and PIN1) at 10x across every core on the slide. Two things make that useful for your own workflow. Because PanCK marks the epithelial tumor cells, you can build a tumor mask and quantify PIN1 only where the tumor is, rather than averaging signal across stroma that would dilute the result. And because the imager captures whole cores as stitched montages, you read many samples under one consistent acquisition instead of hunting fields by eye. Here that turned a marker into a tumor-specific, per-sample number the authors could line up against patient follow-up. 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