FOXO factors: a matter of life and death.
Forkhead box O-class (FOXO) transcription factors, including FOXO1, FOXO3a and FOXO4, function as tumor-suppressor proteins by inhibiting cell proliferation, promoting apoptotic cell death and protecting cells from DNA damage and oxidative stress. The potency of these functions is regulated tightly by phosphorylation, acetylation and ubiquitination. Emerging evidence indicates that protein levels of FOXO1 are under dual regulation by Ak-mediated phosphorylation and Skp2-mediated ubiquitination. Given that Akt and Skp2 proteins are highly activated in human cancers due to the loss of phosphatase and tensin homolog (PTEN), deregulation of the FOXO1 protein appears to be a promising target for future drug discovery and cancer therapy.
Department of Urology and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Haojie
H
Huang
Donald J
DJ
Tindall
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D051858:Forkhead Transcription Factors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000628:therapy; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational
D051858:Forkhead Transcription Factors