Biology:DCAF11
 Generic protein structure example |
DDB1- and CUL4-associated factor 11 also known as WD Repeat Domain 23 (WDR23) is a protein that in humans is encoded by the DCAF11 gene.
DCAF11 is a WD40 repeat protein, containing seven repeats of the closed circular solenoid protein domain WD40.[1] The WDR23 locus is highly conserved from C. elegans to humans.[2] DCAF11/WDR23 is the E3 ligase that specifically targets proteins for degradation via ubiquitination.[3][4][5] WDR-23 exists in two spatially distinct isoforms produced by alternative splicing, a cytoplasmic WDR-23A and nuclear WDR-23B. Nuclear and cytoplasmic versions of WDR-23 have distinct roles.[6]
Dcaf11 is required for the alternative lengthening of telomeres in mouse embryos[7][8] especially at the 2C and four-cell stages of cleavage. The direct binding of DCAF11 in the region of distal enhancer of Zscan4 gene facilitates KAP1 removal by ubiquitination-mediated degradation, leading to a lower level of the repressive H3K9me3 marks and thus activates 2C-specific gene Zscan4.[8]
References
- ↑ "The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans". Molecular and Cellular Biology 29 (10): 2704–2715. May 2009. doi:10.1128/MCB.01811-08. PMID 19273594.
- ↑ "Characterization of skn-1/wdr-23 phenotypes in Caenorhabditis elegans; pleiotrophy, aging, glutathione, and interactions with other longevity pathways". Mechanisms of Ageing and Development 149: 88–98. July 2015. doi:10.1016/j.mad.2015.06.001. PMID 26056713.
- ↑ "Sp1 is a substrate of Keap1 and regulates the activity of CRL4AWDR23 ubiquitin ligase toward Nrf2". The Journal of Biological Chemistry 296: 100704. 2021. doi:10.1016/j.jbc.2021.100704. PMID 33895141.
- ↑ "CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells". Scientific Reports 7 (1): 1175. April 2017. doi:10.1038/s41598-017-01344-9. PMID 28446751. Bibcode: 2017NatSR...7.1175C.
- ↑ "WDR23 regulates NRF2 independently of KEAP1". PLOS Genetics 13 (4): e1006762. April 2017. doi:10.1371/journal.pgen.1006762. PMID 28453520.
- ↑ "Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates". Scientific Reports 9 (1): 11783. August 2019. doi:10.1038/s41598-019-48286-y. PMID 31409866. Bibcode: 2019NatSR...911783S.
- ↑ "Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells". Cells 11 (3): 456. January 2022. doi:10.3390/cells11030456. PMID 35159266.
- ↑ 8.0 8.1 "Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells". Cell Stem Cell 28 (4): 732–747.e9. April 2021. doi:10.1016/j.stem.2020.11.018. PMID 33357405.
Further reading
- "WDR23 regulates the expression of Nrf2-driven drug-metabolizing enzymes". Drug Metabolism and Pharmacokinetics 35 (5): 441–455. October 2020. doi:10.1016/j.dmpk.2020.06.007. PMID 32839090.
- "DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras". Journal of the American Chemical Society 143 (13): 5141–5149. April 2021. doi:10.1021/jacs.1c00990. PMID 33783207.
- "Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells". Cell Stem Cell 28 (4): 732–747.e9. April 2021. doi:10.1016/j.stem.2020.11.018. PMID 33357405.
- "Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle". Cell Reports 37 (6): 109987. November 2021. doi:10.1016/j.celrep.2021.109987. PMID 34758320.
- "Chlorogenic Acid Activates Nrf2/SKN-1 and Prolongs the Lifespan of Caenorhabditis elegans via the Akt-FOXO3/DAF16a-DDB1 Pathway and Activation of DAF16f". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 77 (8): 1503–1516. August 2022. doi:10.1093/gerona/glac062. PMID 35279029.
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