PMID: 32973917 RLIMS-P 2 Check other iTextMine results Issue Report
Title
| 1. | XMU-MP-1 induces growth arrest in a model human mini-organ and antagonises cell cycle-dependent paclitaxel cytotoxicity. |
Abstract
| 2. | Background: XMU-MP-1 is an inhibitor of the Hippo pathway kinases MST1/2 and has been shown to promote the downstream activation of the pro-proliferative, pro-regenerative and anti-apoptotic transcriptional regulator YAP1. |
| 3. | We tested whether XMU-MP-1 can activate YAP1 in a model human mini-organ, namely the hair follicle, to determine whether it can be pharmacologically exploited to promote regeneration in the hair follicle as a novel strategy to treat pathological hair loss disorders. |
| 4. | Results: XMU-MP-1 treatment inhibited MOB1 phosphorylation but did not increase active YAP1 in the hair follicle. |
| 5. | Rather than promote proliferation, XMU-MP-1 serendipitously decreased the number of Ki-67+, EdU+ and phospho histone H3+ hair matrix keratinocytes and antagonised the cytotoxic effects of paclitaxel. |
| 6. | Conclusions: XMU-MP-1 perturbs epithelial cell cycle progression in a model human mini-organ. |
| 7. | This may arise as an off-target effect, especially when XMU-MP-1 has been described to strongly inhibit 21 additional kinases beyond MST1/2. |
| 8. | Therefore, whilst these effects may be dependent on tissue context, researchers should exercise caution when interpreting the effects of XMU-MP-1, especially in tissues with actively proliferating cell populations. |
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Legend: SUBSTRATE KINASE INTERACTANT SITE GENE MIRNA ANOMALY EXPRESSION DISEASE OUTCOME/RESPONSE SR_DRUG DRUG CELL TRIGGER Normalized
Tool: RLIMS-P
| PTM enzyme | Substrate | Site | Sentence |
|---|---|---|---|
| MOB1 (Q9H8S9) | 4 | ||
| histone H3+ | 5 |