Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein
encoded by the FOXO3 gene.FOXO3 belongs to the O subclass of the
forkhead family of transcription factors which are characterized by a
distinct fork head DNA-binding domain. There are three other FoxO
family members in humans, FOXO1, FOXO4 and FOXO6. These transcription
factors share the ability to be inhibited and translocated out of the
nucleus on phosphorylation by proteins such as Akt/PKB in the PI3K
signaling pathway (aside from FOXO6, which may be constitutively
nuclear). Other post-translational modifications including acetylation
and methylation are seen and can result in increased or altered FOXO3a
activity.The use of FOXO3a knockout mice has revealed a diverse range
of functions in both health and disease, namely infertility,
lymphoproliferation, adenoma, organ inflammation, metabolism etc.Yu &
Fellows et al. (2018) demonstrated that FOXO3a activation in vascular
smooth muscle cells induces prominent apoptosis and extracellular
matrix breakdown in vitro and exacerbates atherosclerosis and vascular
remodelling in vivo. Also, these processes were at least partially
dependent on MMP-13, as shown by siRNA knockdown and specific
pharmacological inhibition. Further experiments also revealed MMP-13
as a novel, bona fide transcriptional target gene of FOXO3a in VSMCs.
encoded by the FOXO3 gene.FOXO3 belongs to the O subclass of the
forkhead family of transcription factors which are characterized by a
distinct fork head DNA-binding domain. There are three other FoxO
family members in humans, FOXO1, FOXO4 and FOXO6. These transcription
factors share the ability to be inhibited and translocated out of the
nucleus on phosphorylation by proteins such as Akt/PKB in the PI3K
signaling pathway (aside from FOXO6, which may be constitutively
nuclear). Other post-translational modifications including acetylation
and methylation are seen and can result in increased or altered FOXO3a
activity.The use of FOXO3a knockout mice has revealed a diverse range
of functions in both health and disease, namely infertility,
lymphoproliferation, adenoma, organ inflammation, metabolism etc.Yu &
Fellows et al. (2018) demonstrated that FOXO3a activation in vascular
smooth muscle cells induces prominent apoptosis and extracellular
matrix breakdown in vitro and exacerbates atherosclerosis and vascular
remodelling in vivo. Also, these processes were at least partially
dependent on MMP-13, as shown by siRNA knockdown and specific
pharmacological inhibition. Further experiments also revealed MMP-13
as a novel, bona fide transcriptional target gene of FOXO3a in VSMCs.
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