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NBME 21 Answers
The FOXO transcription factor responds to insulin ...
Nuclear/cytoplasmic shuttling: yes;
Serine phosphorylation: yes
Ubiquitin-mediated proteolysis: no
Thank you for your explanation!
One question: How about the serine phosphorylation? Is it answered by pure memorization that the FOXO TF is serine phosphorylated, or is it a general fact that all TF's are serine-threonine phosphorylated?
I'm not sure, but it may be as simple as this: ubiquitin-mediated proteolysis is irreversible, but both N/C shuttling and phosphorylation are generally reversible processes.
I also guessed that FOXO must be a part of the PI3K pathway, since insulin regulates metabolism through PI3K and the question stem specifically mentions that. Phosphorylation is a major part of that pathway, so even indirectly phosphorylation would regulate FOXO. Frustrating question.
According to wikipedia (https://en.wikipedia.org/wiki/FOXO1) phosphorylation of FOXO1 is irreversible. This is referring to phosphorylation of serine residues on FOXO by Akt, which occurs in response to insulin. But the NBME answer suggests it's reversible. What's up?
i think youre correct cause ubiquitin mediated proteolyis is an irreversible step.