The SCFFBXO28 ubiquitin ligase coordinates CDK activity with MYC-mediated transcription in the cell cycle and predicts poor survival in breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36112 | GEO | 2013/02/28
SECONDARY ACCESSION(S): PRJNA152993
REPOSITORIES: GEO
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Project description:Investigation of differentially expressed genes in human HCT116 cells after knockdown of FBXO28 for 16h and 36h. FBXO28 knockdown and control HCT116 cells. 4 replicates per time point (16h, 36h), including dye swaps.
2013-02-28 | E-GEOD-36112 | biostudies-arrayexpress
Project description:Investigation of differentially expressed genes in human HCT116 cells after knockdown of FBXO28 for 16h and 36h. FBXO28 knockdown and control HCT116 cells. 4 replicates per time point (16h, 36h), including dye swaps.
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Project description: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.
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