TY - JOUR
T1 - Regulation of FOXO protein stability via ubiquitination and proteasome degradation
AU - Huang, Haojie
AU - Tindall, Donald J.
N1 - Funding Information:
This work was partially supported by Stony Brook University School of Medicine and by grants from the National Institutes of Health ( CA134514 and CA130908 ) and the Department of Defense ( W81XWH-07-1-0137 and W81XWH-09-1-622 ) to H.H., and the National Cancer Institute ( CA125747 , CA121277 and CA091956 ) and The T.J. Martell Foundation to D.J.T.
PY - 2011/11
Y1 - 2011/11
N2 - Forkhead box O-class (FOXO) proteins are evolutionally conserved transcription factors. They belong to a family of proteins consisting of FOXO1, FOXO3a, FOXO4 and FOXO6 in humans. Increasing evidence suggests that FOXO proteins function as tumor suppressors by transcriptionally regulating expression of genes involved in cell cycle arrest, apoptosis, DNA repair and oxidative stress resistance. Activation of various protein kinases, including Akt, IκB kinase (IKK) and ERK, leads to phosphorylation of FOXO proteins and their ubiquitination mediated by E3 ligases such as SKP2 and MDM2 in human primary tumors and cancer cell lines. As a result, the tumor suppressor functions of FOXO proteins are either diminished or abrogated due to their ubiquitination-proteasome degradation, thereby favoring cell transformation, proliferation and survival. Thus, ubiquitination and proteasome degradation of FOXO proteins play an important role in tumorigenesis and represent a viable target for cancer treatment. This article is part of a Special Issue entitled: PI3K-AKT-FoxO axis in cancer and aging.
AB - Forkhead box O-class (FOXO) proteins are evolutionally conserved transcription factors. They belong to a family of proteins consisting of FOXO1, FOXO3a, FOXO4 and FOXO6 in humans. Increasing evidence suggests that FOXO proteins function as tumor suppressors by transcriptionally regulating expression of genes involved in cell cycle arrest, apoptosis, DNA repair and oxidative stress resistance. Activation of various protein kinases, including Akt, IκB kinase (IKK) and ERK, leads to phosphorylation of FOXO proteins and their ubiquitination mediated by E3 ligases such as SKP2 and MDM2 in human primary tumors and cancer cell lines. As a result, the tumor suppressor functions of FOXO proteins are either diminished or abrogated due to their ubiquitination-proteasome degradation, thereby favoring cell transformation, proliferation and survival. Thus, ubiquitination and proteasome degradation of FOXO proteins play an important role in tumorigenesis and represent a viable target for cancer treatment. This article is part of a Special Issue entitled: PI3K-AKT-FoxO axis in cancer and aging.
KW - FOXO
KW - Forkhead
KW - Proteasome
KW - Tumor suppressor
KW - Tumorigenesis
KW - Ubiquitination
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U2 - 10.1016/j.bbamcr.2011.01.007
DO - 10.1016/j.bbamcr.2011.01.007
M3 - Review article
C2 - 21238503
AN - SCOPUS:80052968161
SN - 0167-4889
VL - 1813
SP - 1961
EP - 1964
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 11
ER -