We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation.

Forkhead transcription factors FOXO1 (FKHR), FOXO3a (FKHRL1), and FOXO4 (AFX) play a pivotal role in tumor suppression by inducing growth arrest and apoptosis. Loss of function of these factors due to phosphorylation and proteasomal degradation has been implicated in cell transformation and malignancy. However, the ubiquitin ligase necessary for the ubiquitination of the FOXO factors and the relevance of this regulation to tumorigenesis have not been characterized. Here we demonstrate that Skp2, an oncogenic subunit of the Skp1/Cul1/F-box protein ubiquitin complex, interacts with, ubiquitinates, and promotes the degradation of FOXO1. This effect of Skp2 requires Akt-specific phosphorylation of FOXO1 at Ser-256. Moreover, expression of Skp2 inhibits transactivation of FOXO1 and abolishes the inhibitory effect of FOXO1 on cell proliferation and survival. Furthermore, expression of the FOXO1 protein is lost in a mouse lymphoma model, where Skp2 is overexpressed. These data suggest that the Skp2-promoted proteolysis of FOXO1 plays a key role in tumorigenesis.

Pubmed ID: 15668399 RIS Download

Mesh terms: 3T3 Cells | Animals | COS Cells | Cell Cycle Proteins | Cercopithecus aethiops | Cyclin-Dependent Kinase Inhibitor p27 | Forkhead Box Protein O1 | Forkhead Transcription Factors | Humans | Lymphoma | Membrane Proteins | Mice | Mice, Knockout | Phosphoproteins | Recombinant Fusion Proteins | S-Phase Kinase-Associated Proteins | T-Lymphocytes | Transcription Factors | Transfection | Tumor Suppressor Proteins | Ubiquitin

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: DK60920
  • Agency: NIDDK NIH HHS, Id: R01 DK060920
  • Agency: NIDDK NIH HHS, Id: DK65236
  • Agency: NCI NIH HHS, Id: CA91956
  • Agency: NCI NIH HHS, Id: P50 CA091956
  • Agency: NIDDK NIH HHS, Id: R01 DK065236

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.