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2013-07

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cc-by (c) Cepeda, Diana et al., 2013
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/120581

CDK‐mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC‐driven transcription and tumourigenesis and predicts poor survival in breast cancer

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Recurs relacionat

https://doi.org/10.1002/emmm.201202341

Resum

SCF (Skp1/Cul1/F‐box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F‐box protein, FBXO28 that controls MYC‐dependent transcription by non‐proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2‐mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F‐box mutant unable to support MYC ubiquitylation results in an impairment of MYC‐driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK‐FBXO28‐MYC axis as a potential molecular drug target in MYC‐driven cancers, including breast cancer.

Matèries

Càncer de mama, Ubiqüitina, Proteïnes quinases, Cicle cel·lular

Matèries (anglès)

Breast cancer, Ubiquitin, Protein kinases, Cell cycle

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Col·leccions

Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

CEPEDA, Diana, NG, Hwee-fang, SHARIFI, Hamid reza, MAHMOUDI, Salah, SOTO CERRATO, Vanessa, FREDLUND, Erik, MAGNUSSON, Kristina, NILSSON, Helen, MALYUKOVA, Alena, RANTALA, Juha, KLEVEBRING, Daniel, VIÑALS CANALS, Francesc, BHASKARAN, Nimesh, ZAKARIA, Siti mariam, RAHMANTO, Aldwin suryo, GROTEGUT, Stefan, NIELSEN, Michael lund, SZIGYARTO, Cristina al-khalili, SUN, Dahui, LERNER, Mikael, NAVANI, Sanjay, WIDSCHWENDTER, Martin, UHLÉN, Mathias, JIRSTRÖM, Karin, PONTÉN, Fredrik, WOHLSCHLEGEL, James, GRANDÉR, Dan, SPRUCK, Charles, LARSSON, Lars-gunnar, SANGFELT, Olle. CDK‐mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC‐driven transcription and tumourigenesis and predicts poor survival in breast cancer. _EMBO Molecular Medicine_. 2013. Vol. 5, núm. 7, pàgs. 1067-1086. [consulta: 20 de gener de 2026]. ISSN: 1757-4676. [Disponible a: https://hdl.handle.net/2445/120581]

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