| Structural highlights
Disease
[FBX11_HUMAN] Vitiligo. Defects in FBXO11 may be a cause of diffuse large B-cell lymphoma by allowing the accumulation of BCL6, an oncoprotein that has a critical role in lymphomas.[1]
Function
[FBX11_HUMAN] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. The SCF(FBXO11) complex mediates ubiquitination and degradation of BCL6, thereby playing a role in the germinal center B-cells terminal differentiation toward memory B-cells and plasma cells. The SCF(FBXO11) complex also mediates ubiquitination and degradation of DTL, an important step for the regulation of TGF-beta signaling, cell migration and the timing of the cell-cycle progression and exit. Binds to and neddylates phosphorylated p53/TP53, inhibiting its transcriptional activity. SCF(FBXO11) does not seem to direct ubiquitination of p53/TP53.[2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket.
Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.,Munoz-Escobar J, Kozlov G, Gehring K Protein Sci. 2017 Jul 10. doi: 10.1002/pro.3227. PMID:28691247[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Duan S, Cermak L, Pagan JK, Rossi M, Martinengo C, di Celle PF, Chapuy B, Shipp M, Chiarle R, Pagano M. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012 Jan 5;481(7379):90-3. doi: 10.1038/nature10688. PMID:22113614 doi:https://dx.doi.org/10.1038/nature10688
- ↑ Abida WM, Nikolaev A, Zhao W, Zhang W, Gu W. FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity. J Biol Chem. 2007 Jan 19;282(3):1797-804. Epub 2006 Nov 9. PMID:17098746 doi:https://dx.doi.org/10.1074/jbc.M609001200
- ↑ Duan S, Cermak L, Pagan JK, Rossi M, Martinengo C, di Celle PF, Chapuy B, Shipp M, Chiarle R, Pagano M. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012 Jan 5;481(7379):90-3. doi: 10.1038/nature10688. PMID:22113614 doi:https://dx.doi.org/10.1038/nature10688
- ↑ Rossi M, Duan S, Jeong YT, Horn M, Saraf A, Florens L, Washburn MP, Antebi A, Pagano M. Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase. Mol Cell. 2013 Mar 28;49(6):1159-66. doi: 10.1016/j.molcel.2013.02.004. Epub 2013, Mar 7. PMID:23478441 doi:https://dx.doi.org/10.1016/j.molcel.2013.02.004
- ↑ Abbas T, Mueller AC, Shibata E, Keaton M, Rossi M, Dutta A. CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. Mol Cell. 2013 Mar 28;49(6):1147-58. doi: 10.1016/j.molcel.2013.02.003. Epub 2013, Mar 7. PMID:23478445 doi:https://dx.doi.org/10.1016/j.molcel.2013.02.003
- ↑ Abbas T, Keaton M, Dutta A. Regulation of TGF-beta signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2. Cell Cycle. 2013 Jul 15;12(14):2175-82. doi: 10.4161/cc.25314. PMID:23892434 doi:https://dx.doi.org/10.4161/cc.25314
- ↑ Horn M, Geisen C, Cermak L, Becker B, Nakamura S, Klein C, Pagano M, Antebi A. DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation. Dev Cell. 2014 Mar 31;28(6):697-710. doi: 10.1016/j.devcel.2014.01.028. Epub 2014, Mar 6. PMID:24613396 doi:https://dx.doi.org/10.1016/j.devcel.2014.01.028
- ↑ Munoz-Escobar J, Kozlov G, Gehring K. Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding. Protein Sci. 2017 Jul 10. doi: 10.1002/pro.3227. PMID:28691247 doi:https://dx.doi.org/10.1002/pro.3227
|
