The INDIVIDUALIST

A Wiki about biochemical individuality

Nutrigenomics

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Description

Chromosome: 13; Location: 13q14.1

This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma.

Discussion

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. (1)

FOXO factors are important for glucocorticoid-stimulated hPDK4 expression (2)

Organisms adjust their rate of growth depending on the availability of nutrients. Thus, when environmental conditions limit nutrients, growth is slowed and is only restored after food again becomes abundant. Many aspects of the molecular mechanisms that govern this complex control system remain unknown. However, it has been shown that the insulin/IGF-1 (insulin-like growth factor 1) receptor pathway, together with the FOXO family of transcription factors, play an important role in this process. Recent studies with the fruit fly Drosophila melanogaster have provided new insights into the regulatory circuitry that controls both growth and gene expression in response to nutrient availability. (3)

Links

References


1. Huang H, Tindall DJ. FOXO factors: a matter of life and death. Future Oncol. 2006 Feb;2(1):83-9.

2. Kwon HS, Huang B, Unterman TG, Harris RA. Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors.Diabetes. 2004 Apr;53(4):899-910

3. Puig O, Tjian R. Nutrient availability and growth: regulation of insulin signaling by dFOXO/FOXO1. Cell Cycle. 2006 Mar;5(5):503-5. Epub 2006 Mar 1.

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