2k86

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Template:STRUCTURE 2k86

Contents

Solution Structure of FOXO3a Forkhead domain

Template:ABSTRACT PUBMED 18824006

Disease

[FOXO3_HUMAN] Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with MLL/HRX.

Function

[FOXO3_HUMAN] Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation.[1][2][3]

About this Structure

2k86 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Wang F, Marshall CB, Yamamoto K, Li GY, Plevin MJ, You H, Mak TW, Ikura M. Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53. J Mol Biol. 2008 Dec 19;384(3):590-603. Epub 2008 Sep 18. PMID:18824006 doi:http://dx.doi.org/10.1016/j.jmb.2008.09.025
  1. ↑ Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999 Mar 19;96(6):857-68. PMID:10102273
  2. ↑ Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006 Jun 2;125(5):987-1001. PMID:16751106 doi:S0092-8674(06)00559-9
  3. ↑ Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, Burgering BM, Bushell M, Rosenwald A, Eilers M. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011 Feb 18;41(4):445-57. doi: 10.1016/j.molcel.2011.01.023. PMID:21329882 doi:10.1016/j.molcel.2011.01.023

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