support the site ⋅ become a member ⋅ unscramble the egg
free120  nbme24  nbme23  nbme22  nbme21  nbme20  nbme19  nbme18  nbme17  nbme16  nbme15  nbme13 

NBME 21 Answers

nbme21/Block 4/Question#4 (56.5 difficulty score)
The FOXO transcription factor responds to ...
Nuclear/cytoplasmic shuttling: yes;
Serine phosphorylation: yes
Ubiquitin-mediated proteolysis: no


Login to comment/vote.

 +12  upvote downvote
submitted by calcium196(11),
unscramble the site ⋅ become a member ($36/month)

-deaiedUtqnitbiimu yoslpostier is nto lryersievb tfecaedf by .sulnnii heT osqntuei ksas rfo blsveerire sawy that niisnul facfets it, nad itiiinbauuntoq lduow lead to enardgtoaid iva ,tpsasoere whhci is ont lvirbe.eers lomc/seilparcuNcayt ignthnus esakm senes seubace OOXF si a pctnnrasiirot orftc,a os ti tnac’ od ist bjo fi ti si ni teh t!oalscymp

meningitis  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? +  
tsl19  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. +  
didelphus  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. +9  
niboonsh  yes, FOXO is affected downstream of the activation of PI3K. This is a really good video that explains the whole cascade +1  
alexb  According to wikipedia ( 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? +1  
almondbreeze  could wiki be wrong on phosphorylation being irreversible? according to this article, it is a reversible process: regulation of FoxO transcription factors by reversible phosphorylation and acetylation ( some wiki info, however, is helpful : In its un-phosphorylated state, FOXO1 is localized to the nucleus, where it binds to the insulin response sequence located in the promoter for glucose 6-phosphatase and increases its rate of transcription. FOXO1, through increasing transcription of glucose-6-phosphatase, indirectly increases the rate of hepatic glucose production.[19] However, when FOXO1 is phosphorylated by Akt on Thr-24, Ser-256, and Ser-319, it is excluded from the nucleus, where it is then ubiquitinated and degraded. The phosphorylation of FOXO1 by Akt subsequently decreases the hepatic glucose production through a decrease in transcription of glucose 6-phosphatase. +  
leaf_house  It seems like the phosphorylation from Akt leads to destruction, but maybe the assumption is that that phosphorylation step (excluding every other step of ubiquitin-proteosome pathway) is reversible, where proteolysis is final. @niboonsh video is good but doesn't split this one. +  

 +7  upvote downvote
submitted by imgdoc(127),
unscramble the site ⋅ become a member ($36/month)

Tshi uintseqo si iansgk oatbu eht nulnisi trrpeeco nertiyos ekasni pahta.yw oS keta it rmfo ,ereht

  1. eTh trioshppoonhlay fo eht RIS vastciate a iasgln cdtusitnanro cdesaac atht dlesa to teh actotviian fo hroet knaseis as llwe sa rstincotrnaip otcarfs hatt iatdmee het rllacruaelitn esftefc fo oleNaycClrsmat/upic tgnlhstiu - esy rbrvi()lesee

  2. eeinhoerTeSrnin/ iseansk era aosl nwnok ot eurecd het ttcivaiy of .iiunnsl - yes le(vser)rebi

  3. ubUiqtiin - temddiae lipsosretyo - on ont( evrrsbl),eie dna loas iilnusn lyoaltlamicbe ceeasrnsi prontei syshtiens so it tn'sedo mchta hatw inisuln osde s.anywya

coetcrr me fi m'I .rowgn

usmle11a  i think youre correct cause ubiquitin mediated proteolyis is an irreversible step. +1  

 +4  upvote downvote
submitted by hello(246),
unscramble the site ⋅ become a member ($36/month)

Teh Q etsm esastt OFOX is a niarittncpros aroftc taht edsrspon to ulnsini lngainisg by rlgatnei hte tpcnirroisnat fo obmicleat eesng t;g&-- t,ofehreer OXFO si a riinactoptrsn acroft dlivveon ni soilet.mabm shiT ludohs aemk esesn bcsueae tnrsceorni-ipleu civttaoain has a elro ni guargieltn mtmel.bsoia

Tihs Q ksas otaub bveslierer swya taht innilsu seatgreu OXFO ansttcrprnio rtoacf itv.iycta

i-tmtaUqnbiedueidi sliotsyorpe is irbrleisveer. aielmtiEn lal cechios tepcex fro ,B D, dan .H

r-uelsIitnorcesnp onnfituc uhothrg P3KI sngai.nlgi PI3K ngsiialgn esvovnli hhrosatppyinloo fo ensrei t--&g; esirne plooarpohshtyni si a beveerrlsi erpscos. itElmiena H. IF:Y enmopinot/air idac sotpolaihponhyr is slywaa rl.eibesrev

uoY aer ltef wiht hcoeics B nad .D

FXOO si a arocritnsnpit oatfcr &;--tg stonrrnitcipa frctosa teamied egen yvaictit yb thtignlus etewben het lcayospmt nad euculs.n ggRlnueait het aotconli of XOOF innaipsttorrc trcaof i.(.e ocmslpayt vs. u)enucsl lwil eetofehrr lievryrseb laeuomtd tO-aFXOimddee ctombeila enge vitita.yc

hTsi elesav uyo wiht eth cotrecr e:arswn hiCcoe B.

adong  A better way to think about it is insulin acts through MAPK which is a serine/threonine kinase +  

unscramble the site ⋅ become a member ($36/month)

Sneeir isooppyhhrotnla liwl deurce lunsn'isi acftsf.e tI sact on het itryseno na.kesi