CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer

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CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. / Cepeda, Diana; Ng, Hwee-Fang; Sharifi, Hamid Reza; Mahmoudi, Salah; Cerrato, Vanessa Soto; Fredlund, Erik; Magnusson, Kristina; Nilsson, Helén; Malyukova, Alena; Rantala, Juha; Klevebring, Daniel; Viñals, 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.

In: E M B O Molecular Medicine (Online), Vol. 5, No. 7, 03.07.2013, p. 1067-1086.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Cepeda, D, Ng, H-F, Sharifi, HR, Mahmoudi, S, Cerrato, VS, Fredlund, E, Magnusson, K, Nilsson, H, Malyukova, A, Rantala, J, Klevebring, D, Viñals, F, Bhaskaran, N, Zakaria, SM, Rahmanto, AS, Grotegut, S, Nielsen, ML, Szigyarto, CA-K, Sun, D, Lerner, M, Navani, S, Widschwendter, M, Uhlén, M, Jirström, K, Pontén, F, Wohlschlegel, J, Grandér, D, Spruck, C, Larsson, L-G & Sangfelt, O 2013, 'CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer', E M B O Molecular Medicine (Online), vol. 5, no. 7, pp. 1067-1086. https://doi.org/10.1002/emmm.201202341

APA

Cepeda, D., Ng, H-F., Sharifi, H. R., Mahmoudi, S., Cerrato, V. S., Fredlund, E., Magnusson, K., Nilsson, H., Malyukova, A., Rantala, J., Klevebring, D., Viñals, F., Bhaskaran, N., Zakaria, S. M., Rahmanto, A. S., Grotegut, S., Nielsen, M. L., Szigyarto, C. A-K., Sun, D., ... Sangfelt, O. (2013). CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. E M B O Molecular Medicine (Online), 5(7), 1067-1086. https://doi.org/10.1002/emmm.201202341

Vancouver

Cepeda D, Ng H-F, Sharifi HR, Mahmoudi S, Cerrato VS, Fredlund E et al. CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. E M B O Molecular Medicine (Online). 2013 Jul 3;5(7):1067-1086. https://doi.org/10.1002/emmm.201202341

Author

Cepeda, Diana ; Ng, Hwee-Fang ; Sharifi, Hamid Reza ; Mahmoudi, Salah ; Cerrato, Vanessa Soto ; Fredlund, Erik ; Magnusson, Kristina ; Nilsson, Helén ; Malyukova, Alena ; Rantala, Juha ; Klevebring, Daniel ; Viñals, 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 SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. In: E M B O Molecular Medicine (Online). 2013 ; Vol. 5, No. 7. pp. 1067-1086.

Bibtex

@article{1efc604634124ad0a5c9a1e41667efd2,
title = "CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer",
abstract = "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. SCF(FBXO28) 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 SCF(FBXO28) 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.",
author = "Diana Cepeda and Hwee-Fang Ng and Sharifi, {Hamid Reza} and Salah Mahmoudi and Cerrato, {Vanessa Soto} and Erik Fredlund and Kristina Magnusson and Hel{\'e}n Nilsson and Alena Malyukova and Juha Rantala and Daniel Klevebring and Francesc Vi{\~n}als and Nimesh Bhaskaran and Zakaria, {Siti Mariam} and Rahmanto, {Aldwin Suryo} and Stefan Grotegut and Nielsen, {Michael Lund} and Szigyarto, {Cristina Al-Khalili} and Dahui Sun and Mikael Lerner and Sanjay Navani and Martin Widschwendter and Mathias Uhl{\'e}n and Karin Jirstr{\"o}m and Fredrik Pont{\'e}n and James Wohlschlegel and Dan Grand{\'e}r and Charles Spruck and Lars-Gunnar Larsson and Olle Sangfelt",
note = "{\textcopyright} 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.",
year = "2013",
month = jul,
day = "3",
doi = "10.1002/emmm.201202341",
language = "English",
volume = "5",
pages = "1067--1086",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "7",

}

RIS

TY - JOUR

T1 - CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer

AU - Cepeda, Diana

AU - Ng, Hwee-Fang

AU - Sharifi, Hamid Reza

AU - Mahmoudi, Salah

AU - Cerrato, Vanessa Soto

AU - Fredlund, Erik

AU - Magnusson, Kristina

AU - Nilsson, Helén

AU - Malyukova, Alena

AU - Rantala, Juha

AU - Klevebring, Daniel

AU - Viñals, Francesc

AU - Bhaskaran, Nimesh

AU - Zakaria, Siti Mariam

AU - Rahmanto, Aldwin Suryo

AU - Grotegut, Stefan

AU - Nielsen, Michael Lund

AU - Szigyarto, Cristina Al-Khalili

AU - Sun, Dahui

AU - Lerner, Mikael

AU - Navani, Sanjay

AU - Widschwendter, Martin

AU - Uhlén, Mathias

AU - Jirström, Karin

AU - Pontén, Fredrik

AU - Wohlschlegel, James

AU - Grandér, Dan

AU - Spruck, Charles

AU - Larsson, Lars-Gunnar

AU - Sangfelt, Olle

N1 - © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

PY - 2013/7/3

Y1 - 2013/7/3

N2 - 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. SCF(FBXO28) 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 SCF(FBXO28) 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.

AB - 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. SCF(FBXO28) 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 SCF(FBXO28) 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.

U2 - 10.1002/emmm.201202341

DO - 10.1002/emmm.201202341

M3 - Journal article

C2 - 23776131

VL - 5

SP - 1067

EP - 1086

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4676

IS - 7

ER -

ID: 57416710