| First Author | Xie G | Year | 2020 |
| Journal | Dev Cell | Volume | 55 |
| Issue | 6 | Pages | 707-722.e9 |
| PubMed ID | 33321102 | Mgi Jnum | J:300522 |
| Mgi Id | MGI:6503754 | Doi | 10.1016/j.devcel.2020.11.012 |
| Citation | Xie G, et al. (2020) Centrosomal Localization of RXRalpha Promotes PLK1 Activation and Mitotic Progression and Constitutes a Tumor Vulnerability. Dev Cell 55(6):707-722.e9 |
| abstractText | Retinoid X receptor alpha (RXRalpha), a nuclear receptor of transcription factor, controls various physiological and pathological pathways including cellular growth, proliferation, differentiation, and apoptosis. Here, we report that RXRalpha is phosphorylated at its N-terminal A/B domain by cyclin-dependent kinase 1 (Cdk1) at the onset of mitosis, triggering its translocation to the centrosome, where phosphorylated-RXRalpha (p-RXRalpha) interacts with polo-like kinase 1 (PLK1) through its N-terminal A/B domain by a unique mechanism. The interaction promotes PLK1 activation, centrosome maturation, and mitotic progression. Levels of p-RXRalpha are abnormally elevated in cancer cell lines, during carcinogenesis in animals, and in clinical tumor tissues. An RXRalpha ligand XS060, which specifically inhibits p-RXRalpha/PLK1 interaction but not RXRalpha heterodimerization, promotes mitotic arrest and catastrophe in a tumor-specific manner. These findings unravel a transcription-independent action of RXRalpha at the centrosome during mitosis and identify p-RXRalpha as a tumor-specific vulnerability for developing mitotic drugs with improved therapeutic index. |
