5vmd

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]}

See Also

• Ubiquitin protein ligase 3D structures

References

1. ↑ 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:http://dx.doi.org/10.1038/nature10688
2. ↑ 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:http://dx.doi.org/10.1074/jbc.M609001200
3. ↑ 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:http://dx.doi.org/10.1038/nature10688
4. ↑ 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:http://dx.doi.org/10.1016/j.molcel.2013.02.004
5. ↑ 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:http://dx.doi.org/10.1016/j.molcel.2013.02.003
6. ↑ 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:http://dx.doi.org/10.4161/cc.25314
7. ↑ 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:http://dx.doi.org/10.1016/j.devcel.2014.01.028